On Myopia

Joined
Nov 26, 2013
Messages
7,370
I'm a midwesterner.
I would think—based on the tentative model—that less amounts of the more refractive methylimidazalone would be formed on the euglycemic state. This should decrease the refractive index of the lens after a few weeks—or however long it takes to form a new lens. I would also think the velocity of the change would depend on where exactly the rhodopsin is located relative to the focal point, and there being less change in those concomitantly wearing glasses. If the retina remodels faster than the lens, can keep‐up with the varying refractive index, you could perhaps expect less noticeable change.

Raising methylglyoxal to increase the refractive index might could be a thing to try. The two best ways for doing this, in my opinion, are by using a glyoxylase I inhibitor and/or L-threonine. Paul Thornally has written extensively on the glyoxylase system, and has published an excellent review. It basically consists of two enzymes—glyoxylase I and glyoxylase II—which transform endogenous methylglyoxal into lactate in a step-wise fashion, in series. The first step is methylglyoxal spontaneously associating with the thiol of glutathione: this new complex is the substrate for glyoxlase I, which simply isomerizes this and letting glyoxylase II do the rest—releasing lactate and regenerating glutathione. Inhibiting this enzyme leads to a higher steady‐state methylglyoxal level. The best inhibitors that I've seen were β-lapachone and lapachol, both found in pau d'arco. These molecules have the lowest ki values (~5·μM), and are both small and soluble—making them better options than the others. Curcumin—for instance—inhibits in vitro isolated glyoxylase I to a similar degree, but can barely penetrate the cell; in fact, it's barely absorbed at all. All the pharmacokinetic studies measure essentially zero blood levels after consuming even gram amounts.

But probably just as good for raising methylglyoxal is L-threonine. This is the only amino acid which becomes methylglyoxal directly in high amounts—a process process even mentioned by Vander Jagt in an article cited above.

"Methylglyoxal can also be made from aminoacetone during the catabolism of L-threonine (6)." —Vander Jagt

He cited (6) an article published in 1959, but there are better ones out there. The article he cites isn't experimental proof, but I've read articles that do actually prove this.

And it's easy to see why this should happen: After decarboxylation, threonine becomes aminoacetone; this is then acted-upon by monoamine oxidase forming methylglyoxal:

[pic]

The best way (and safest way) for raising methylglyoxal levels, in my opinion, is by consuming pau d'arco tea—in a french press, with coffee—while taking anywhere between 500 – 3,000 milligrams of L-threonine per day. Pau d'arco is actually an inner tree bark, like ceylon cinnamon, and tastes somewhat like cinnamon.

Thornalley, Paul J. "The glyoxalase system in health and disease." Molecular aspects of medicine (1993)
Thornalley Paul J. "Inhibitors of glyoxalase I: design, synthesis, inhibitory characteristics and biological evaluation." Biochemical Society transactions (1993)
Vander Jagt, D. L. "Reduction of trioses by NADPH-dependent aldo-keto reductases. Aldose reductase, methylglyoxal, and diabetic complications." Journal of Biological Chemistry (1992)



Well, check‐out the prevalence of refractive change in Asia:

View attachment 7394click to embiggen

I used to think that they wore glasses just to look smart, but.. . . ..but have you seen the List of Chinese inventions on Wikipædia? Not bad, if I may say so myself. The Japanese and Chinese could very well deserve the stereotype.
I think that it must be false, or misleading, in most cases. Hyperglycemia can cause refractive changes in minutes, and aldose reductase inhibitors prevent this from happening. This proves that glycolytic metabolism downstream of aldose reductase can cause refractive changes, and also deftly refutes the osmotic theories since sorbital or triose don't have any higher osmotic potential than glucose itself—or sodium for that matter. Of course, a change in the eyeballs's shape—or the position of the retina—would very likely produce changes in light perception (unless two parameters change simultaneously, thereby off‐setting eachother), but the associations between blood glucose levels are undeniable. This isn't the only way to produce myopia/hyperopia, but I think that's its the primary factor in the majority of cases. For some reason, this idea isn't popular; this could perhaps be the result of politics, or that most people prefer a simpler explanation—or a mix of the two.

You will! Hang in there. We need to read more about rhodopsin, microtubules, and cone cells. . . but not to discount the role of the refractive index of the lens itself—changed through a post‐translational modification or the lens protein crystallin, thereby producing an nonconventional amino acid higher refractive index.

I am willing to bet that we could find scientific articles describing how the morphology and growth rate of retinal cone cells change on exposure to light. These cells need to occupy the space of the focal point of the lens, and play a role in all of this.

Is this Ray Peat talking about the "glycation" of crystallin? I think this is a misleading term, as its too close to "glycosylation;" this almost implies that glucose itself is adding to the protein. This is not the case. Certain trioses are reacting with arginine side‐chains in a cyclicization reaction, in a manner which can probably be best described as a post‐translational modification. Thrornally has shown just recently that that methylglyoxal can induce or suppress DNA→mRNA transcription in this manner—by modifying a transcription factor in cell's nucleus (mSin3A).

And 'glycation' is also misleading for the obvious reason that methylglyoxal can be produced from either glycerol of threonine.

Yao, Dachun. "High glucose increases angiopoietin-2 transcription in microvascular endothelial cells through methylglyoxal modification of mSin3A." Journal of Biological Chemistry (2007)
Wang, Tina. "Exploring post-translational arginine modification using chemically synthesized methylglyoxal hydroimidazolones." Journal of the American Chemical Society (2012)


I had realized a few days ago that I had to look into this, and that glucose must be involved–somehow. When reading about it, it because clear what was going on. This led directly into a more familiar territory form me: the methylglyoxal–arginine adducts, what I find most interesting.
You'd expect this to occur, but γ-crystallin has only eight cysteines; compare that to the twenty arginines. The methylglyoxal–thiol bond is a bit more labile that the condenstation of methylglyoxal and arginine, which forms a species so resilient that it can be detected in urine. Thiol–acyl bonds, as is acetyl–CoA, are routinely formed and cleaved by low-energy enzymes within the body during (fatty acid metabolism). The carbon–sulfur bond isn't one of the strongest, and I'd assume any methylglyoxal–thiol bonds to be transient (as in the case of methylglyoxal–glutathione); sulfur binds most strongly to mercury.

Glutathione is needed to turn methylglyoxal into lactic acid, and can perhaps be considered a cofactor. Glutathione is a prerequisite for the methylgyloxal→lactic acid conversion through the glyoxylase system. High methylglyoxal leads to less-active glutathione as it's occupied by such, on the thiol group. This hasn't been overlooked in attempting to explain how methylglyoxal reverses cancer; it has been speculated that this occupation of glutathione is the primary reason. While it's true that gluationine is needed for mitosis, I think a bit differently: I think that methylglyoxal works mostly by adding to a specific arginine side-chain in NADH-dependent glycolytic enzymes, which all have an arginine which bonds the phosphodiester of it's cofactor—NADH. Arginine is always found at this location in such enzymes in a highly‐intuitive interaction: The fully-positive or ∂-positive charges of arginine—found on the γ-nitrogens—interact noncovalently with the negative oxygen atoms of the phosphodiester—like the well-known 'salt bridge' between glutamate and lysine, for instance. These NADH-dependent enzymes simply cannot bind the cofactor without this arginine, and point-mutational analysis fully confirm this. This would explain why glyolytic rates drop quickly with 3‐bromopyruvate or methylglyoxal: They work on glycolytic enzymes directly by abrogating their ability to bind NADH—their cofactor—by permanently‐modifying a key arginine residue while it's being assembled in the ribosome . . . or shortly thereafter.
That's a very interesting observation, and an interesting graph. Growth hormone does raise insulin, right? leading to lower blood glucose and methylglyoxal—leading then further to a lower percentage of arginine transformed into methylimidazolone resulting in a negative shift of the lens' refractive index.
This is interesting. I know that glutamate and GTP both powerfully influence the polymerization rates of tubulin in vitro, and had a thought that dopamine was perhaps involved in this. If you look at colchicine, you'll realize it has multiple methoxy groups. You may also realize that over 95% of molecules classified as "microtubule inhibitors" have methoxy groups—you can find dozens of examples of this. Dopamine can be methylated on one of the catechol oxygens, leading to methoxytyramine—or methyldopamine (synonymous). The enzyme catechol‐O‐methyltransferase is responsible for doing this, and the low‐activity methionine‐encoding allele of the gene is often correlated with higher IQ. There are dozens of studies on catechol‐O‐methyltransferase and IQ, and methoxytyramine has been implicated in Parkinson's dyskinesia (caused by ingesting too much L-DOPA.)

I don't find it hard to believe that the ratio of dopamine to methyldopamine could influence microtubules in vivo, since the methoxy groups seems almost a prerequisite for a powerful microtubule polymerization inhibitor/destabilizer (see colchicine, methoxyestradiol, and many more.)
Yeah. You'd think that polyunsaturated fatty acids would activate the Randall Cycle, likely through PPARγ upregulating the fatty acid synthase and the β-oxidation enzymes. Too many fatty acids of the wrong type certainly seem capable of throwing someone into 'diabetes mode.' Anything that effects glucose metabolism—or modulates the glyoxylase system—would be expected to modify the refractive index of crystallin. The higher prevalence of myopia among adolescents can perhaps be explained by the action of growth hormone, through raising insulin (Diokene, 2017); and the hyperopia seen in diabetes can certainly by caused by hyperglycemia (Eva, 1982).
I dunno man... long eyeball seems to me like a fitting feature of a vitamin A and light-deficient morphogenesis.
 
OP
Travis

Travis

Member
Joined
Jul 14, 2016
Messages
3,189
XIII. The Cornea

"Of interest is the observation that corneal fluorescence in diabetic patients correlate with the degree of retinopathy, duration of diabetes, and degree of glycemia." ―Candace Sady

The change in refractive index of the lens alone doesn't represent all changes possible, since the cornea has been estimated to contribute two‐thirds of the refractive power of the eye; as such, the cornea would be expected to be a primary determinant in vision changes. The cornea consists primarily of collagen, which has a considerable amount of both arginine and lysine residues. The cornea of the diabetic has also been shown to be modified by 'Maillard products,'—an imprecise historical term used to describe methylgloxal–protein products, coined before they'd been more thoroughly defined.

Sady, C. "Advanced Maillard reaction and crosslinking of corneal collagen in diabetes." Biochemical and biophysical research communications (1995)
And because collagen also contains a considerable amount of lysine, what is found is a diverse array of cyclic methylglyoxal products including pyrimidines, pyrralines, the aforementioned imidizalones, and the indole‐like pentosidine. These can be measured by their fluorescence, and are found higher in diabetics.

myopia13.png


The fluorescence of proteins necessarily correlates with the molar extinction coefficient, and the molar extinction coefficient correlates well with the refractive indices of the individual amino acids.⁽¹⁾⁾⁽²⁾⁽³⁾ Therefore, you're nearly forced to conclude that fluorescence is correlated with refractive index.

(1) Zhao, Huaying. "On the distribution of protein refractive index increments." Biophysical journal (2011)

(2) McMeekin, Thomas L. "Refractive indices of proteins in relation to amino acid composition and specific volume." Biochemical and Biophysical Research Communications (1962)
(3) Kuipers, Bas JH. "Prediction of molar extinction coefficients of proteins and peptides using UV absorption of the constituent amino acids at 214 nm to enable quantitative reverse phase high-performance liquid chromatography− mass spectrometry analysis." Journal of agricultural and food chemistry (2007)

XIV. The Refractive Index of the Cornea

The refractive index of the cornea is around .1400, although this value changes depending on the distance from the optical axis. This value has also been found to vary considerably between subjects, ranging from 1.390 to 1.408.

myopia14.png click to embiggen


Although this might appear to be a small change, this can result in a significant reduction in visual acuity–on the order of dioptres:

"An experimental study demonstrated that a decrease in refractive index from 1.42 to 1.40 produced a hyperopic change of 3.2 dioptres; therefore, a slight change in the refractive index produces a significant hyperopic change." ―Fumiki Okamoto
Patel, Sudi "Refractive index of the human corneal epithelium and stroma." Journal of Refractive Surgery (1995)

XIV. The Cornea and the Lens both Dictate the Light's Path

The cornea is generally modeled as a meniscus‐shaped lens, and the lens itself as a biconvex type. Changes in either one would be expected to produce vision changes, but of opposite effect—they bend light in opposing directions. Myopia could then perhaps be seen either as the result of a decreased refractive index of the protein lens, or an increase in the refractive index of the cornea. That could be why you'll have such disparate accounts such articles such as those from Paul Riordan Eva, Duke Elder, and the article below.


Okamoto, Fumik. "Refractive changes in diabetic patients during intensive glycaemic control." British journal of ophthalmology (2000)
Patients were treated for hyperglycemia with their refractive changes routinely measured—for weeks. Noticeable refraction changes occurred, taking weeks to fully manifest itself. This suggests that new protein synthesis could be the limiting factor.

myopia15.png click to embiggen

Okamoto, undaunted by this massive time lag, attempts to explain these refractive changes—obviously the result of blood glucose changes—by conjuring the osmotic hypothesis.

"However, although glucose freely enters the intracellular space, sorbitol, which is less permeable and harder to metabolise, will remain in the lens longer. The diverence in osmotic pressure results in the influx of water from the aqueous humour into the lens, causing lenticular swelling with hyperopic refractive changes." ―Okamoto

The blood glucose levels correlate well with refractive changes:

myopia16.png

Despite the shortcomings of the osmotic hypothesis, Okamoto must be given credit for trying. Many sources, such as Wikipædia, simply say something vague about 'eye ball' shape. Okamoto observed no changes in eye shape, refuting attempts to explain myopia in that manner.

"During transient hyperopia, no significant changes were observed in the radius of the anterior corneal curvature, axial length, lens thickness, or depth of anterior chamber." ―Okamoto

"Thus, the transient hyperopic changes in diabetic patients during intensive glycaemic control is attributed not to morphological changes in the cornea, axial length, or lens, but to some intraocular change in refraction." ―Okamoto

There are two theories on intraocular changes in refraction so far mentioned: The Osmotic Hypothesis is one; which can't explain why sodium has no effect on refractive changes, blood pressure has no effect on refractive changes, and how refractive changes can happen in mere hours yet take weeks to revert. Theories centered around methylgloxal can easily explain these things.


"Thus, the biological basis of refractive changes in the eyes of diabetic patients has not yet been established and the underlying mechanism is still unknown." ―Okamoto
XV. The Concentration of Methylgloxal in the Human Lens

"The concentration of methylglyoxal in the lenses was ~20 fold higher than in blood samples from normal human subjects." ―Thornally

Renowned methylgloxal expert Paul Thornally has studied methylglyoxal concentrations in the human lens; he has also studied the activities of glyoxylase I & II in the lens.

"In laboratory rats, the lens contained a particularly high level of methylglyoxal, 2·1 nmol (g wet weight)⁻¹, which was increased 116% in experimental diabetes." ―Thornally

"The concentration of methylglyoxal of the 26 human was 1·78 ± 0.84 nmol (g wet weight)⁻¹." ―Thornally


"Methylglyoxal binds and reversibly modifies cystetine, lysine, and arginine residues in proteins. A further slow reaction leads to the irreversible modification of arginine residues in proteins to form an imidazalone derivative which is fluorescent." ―Thornally

Paul J. Thornalley. "Methylglyoxal concentration and glyoxalase activities in the human lens." Experimental eye research (1994)

XVI. Ab Initio Calculation of Crystallin's Refractive Index

The unmodified refraction index of γ-crystallin has been calculated to be 1.88 from the Zhao equations and the table provided with the molecular mass values from Promega, but the refraction index of the entire lens depends on water content. This is a high value for a protein: McMeekin and Groves calculated 1.634 for ribonuclease, 1.609 for pepsin, and 1.593 for β-lactoglobulin (Table II, McMeekin, 1962). The values determined experimentally for these proteins were close, at: 1.630, 1.603, and 1.594, respectively. The close agreement between the predicted and measured values highlights the veracity of this method.

Although calculating the refractive index of a small protein like γ-crystallin is do‐able by hand, I wouldn't suggest calculating anything over 200 amino acids without a computer program such as Microsoft Excel.

Zhao, Huaying. "On the distribution of protein refractive index increments." Biophysical journal (2011)
McMeekin, Thomas L. "Refractive indices of proteins in relation to amino acid composition and specific volume." Biochemical and Biophysical Research Communications (1962)

XVII. The Physical Determinants of Vision

By looking at an illustration of the eye, three primary determinants of visual acuity appear to be: The refractive index of the cornea, the refractive index of the lens, and the position of rhodopsin along the optical axis. The only thing which can explain the sudden onset of hyperglycemic vision changes and resistance towards reversion as osmolarity equilibrates—as well as the undeniable correlation between hyperopia and glucose—appears to be ones centering around methylgloxal, which is found in the lens and can produce changes in both fluorescence and refraction index through well‐established chemical mechanisms.
 
Last edited:
OP
Travis

Travis

Member
Joined
Jul 14, 2016
Messages
3,189
XVIII. Explaining Epidemiological Prevalence

The prevalence of refractive error is geographically variable, an observation which has befuddled all prior attempts at explanation. The greater prevalence observed in India and China cannot simply be explained by the Osmotic Theory. Below are two graphs: one of the geographic prevalence of refractive error, and one of sodium consumption per capita:

myopia17.png myopia21.png click to embiggen

These two can hardly be said to be superimposable. Proponents of the Osmotic Hypothesis may experience transient elation upon seeing China ranked high! on the Global Sodium Intake map, but this will quickly give way to disappointment after glancing at the others—most notably India and Kazakhstan.

Rice intake actually correlates better than anything.

myopia17.png myopia22.png

Since visual acuity is largely determined by refractive index of the cornea, you would expect the production rate of collagen to play a major role. New collagen has lower fluorescence and, hence, refractive index. Collagen is relatively enriched with the amino acids arginine and lysine, which contribute to the formation of the post‐translational fluorescent crosslinks (i.e. pentosidine).

arginine.png lysine.png click to embiggen

The two limiting amino acids of rice happens to be lysine and threonine, a fact that has been known since the '40s. Multiple early rat feeding studies unambiguously prove this to be so. Below are excepts from one such study:


"We believe these results demonstrate that threonine is the second limiting amino in the rice protein." Rosenberg

"This is also in agreement with the more recent amino acid analysis of rice by Kik ('56), which was confirmed in our laboratories. Having established lysine and threonine as the first and second limiting amino acids in rice protein for the growth of the weanling rat, it was of interest to determine if the addition of the next limiting amino acids to the diet supplemented with lysine and threonine would elicit a growth response." Rosenberg

"As seen from table 3, no growth responses were obtained, thus ruling out histidine as the second limiting amino acid." Rosenberg

Rosenberg achieved a slight increase in growth with methionine, isoleucine, and tryptophan—commonly suspected as candidates for position of third limiting amino acid. However, the addition of methionine would be expected to produce growth regardless through the production of polyamines—powerful growth factors suspected to play a role in unfurling DNA in the cell's nucleus. However, studies testing growth rates of rice have failed to demonstrate any significant limiting amino acid besides lysine and threonine.

"The results presented in table 1 (Exp. 1) show that the addition of phenylalanine along with histidine, tryptophan and methionine to a diet containing the higher levels of lysine and threonine (0.4 and 0.5% respectively) did not in any way improve growth over that observed with only lysine and threonine." —Deshpande

"When the remaining essential amino acids arginine, leucine, isoleucine, and valine were added individually together with the amino acids provided for group 5, the liver fat values remained low, but there was still no improvement in growth;" —Deshpande

"Supplementation with methionine and tryptophan did not further improve growth." —Deshpande

Deshpande only used 0.1% DL‐methione—a racemic mixture only half active—while Hans Rosenberg had used 0.3% DL‐methionine. (As a sidenote, John Richie had shown in 1994 that increasing the rat's methionine intake from 0.17% to 0.86% led to a 42% reduction in mean longevity, and weight gain, more than confirming the 30% increase observed by Orentreich one year earlier under near‐identical conditions.)

Since there is a universal agreement that the two limiting amino acids of rice protein are lysine and threonine, you'd expect the map of Global Rice Intake to be nearly synonymous with low lysine intake—an essential amino acid of collagen. If Asians and Indians can be expected to have a lower dietary ratio of lysine and threonine, you'd expect them to have a lower collagen turnover rate—equating to more aged collagen of the cornea consisting of higher pentosidine, methylimidzaole, argpyrimidine, fluorescence, refractive index, and subsequent changes in visual acuity. The high glycemic index of rice (~85) can only be expected to further increase these changes.

"Myopia 20.5 diopter or less in either eye was essentially absent in 5-year-old children, but increased to 36.7% in males and 55.0% in females by age 15. [...] Reduced vision because of myopia is an important public health problem in school-age children in Shunyi District." —Jialiang

Just as important as glucose in determining the refractive change of the lens could be the collagen synthesis rate of the cornea, with reductions being expected to increase the refractive index of the cornea through reduced collagen turnover; more time for post‐translational modifications—or what some would call 'Maillard additions' or 'glycation.' It's well established that fluorescence increases both in diabetes and age, implying that both glucose—through the formation of methylglyoxal and acetol—and collagen turnover both determine corneal fluorescence.


myopia27.png myopia28.png click to embiggen

The change in fluorescence is directly proportional to the change in refractive index.

The genes which encode collagen type I alpha, collagen type II alpha, β-crystallin A4, and insulin‐like growth factor 1 have all been found correlated with myopia—according to geneticist Felicia Hawthorne.


Orentreich, Norman. "Low methionine ingestion by rats extends life span." The Journal of nutrition (1993)
Hawthorne, Felicia. "Convergence of genetic disease association and ocular expression." Duke University (2012)
Richie, John P. "Methionine restriction increases blood glutathione and longevity in F344 rats." The FASEB Journal (1994)
Chang, Shu-Wen. "Changes in corneal autofluorescence and corneal epithelial barrier function with aging." Cornea (1993)
Zhao, Jialiang. "Refractive error study in children: results from Shunyi District, China." American journal of ophthalmology (2000)
Sady, C. "Advanced Maillard reaction and crosslinking of corneal collagen in diabetes." Biochemical and biophysical research communications (1995)
 
Last edited:
OP
Travis

Travis

Member
Joined
Jul 14, 2016
Messages
3,189
@Travis thanks for the good info. Are there and good recommendations to reverse myopia that you have found?
Myopia appears to me, at the moment, to be a difference in refractive index between the cornea and the lens‐(eye).

The cornea is a meniscus lens, and the lens‐(eye) is is a biconcave lens. The cornea is convergent; the lens‐(eye) is divergent. Myopia can either be caused by an increase in the refractive index of the cornea, or a decrease in the refractive index of the lens‐(eye). I think the former difference in refraction is, by far, the more common. It's hard to imagine many scenarios in which the lens would decrease in refractive index.

The cornea is made of collagen: Since aged collagen has a higher refractive index, it follows that naïve collagen would have a lower refractive index. This is more than intuitive; this can be inferred directly from experimental data. This leads to the idea that the refractive index of the cornea can be lowered by increasing the rate of collagen synthesis (perhaps through vitamin C and gelatin).

High blood glucose is expected to either increase the refractive index of the cornea or the lens‐(eye), individually or in tandem: causing either myopia, hyperopia, or no change depending on pharmacokinetics, insulin, and protein synthesis rates. Since the cornea is extracellular, I would expect the cornea to be more liable to the methylgloxal addition reactions consequent of high glucose. For this reason, anything with a high glycemic index should probably be avoided—there are also many other good reasons to avoid such foods.

Reversing myopia could be the Chinese diet in reverse: low glycemic foods with high lysine. The way I view it, myopia is a function of unnaturally‐high glycemic foods amplified by an unnatural dietary amino acid ratio. Not wearing corrective lenses while consuming fruit and collagen seems like it would be the best approach. If you would like to test this thought, perhaps check‐out testimonials of myopia reversals during fasting and Gerson retreats. I think you might find confirmation of this theory by doing so. I'm trying to legitimize all observations with a scientific model, and intend on doing so until it's either modified, falsified, or becomes undeniable Truth to others—the way I see it. Explanations involving rapid eyeball change—or in the depth of the optical cavity—sound absurd, and experimental observations directly contradict it. The osmotic theories are likewise absurd, as they cannot explain why the consumption the more osmotic salt (NaCl) does nothing. (Keep in mind that the osmotic theories were created to explain how sugar causes refractive changes in a time period completely oblivious to methylglyoxal–protein adducts.) I consider these explanations examples of 'lollipop science,' both for their absurdity and their inability to explain the data. In scientific articles about diabetes and refraction changes, you commonly find the word 'paradox'—a word which essentially can be seen as a tacit admission or an incorrect model.

I don't think my theory can be so easily falsified; it reflects the data near‐perfectly. (Optical equations are forthcoming.)

Since gelatin and fruit are Peat‐friendly, I can recommend them with complete impunity here.

I would think the hardest part about reversing myopia lies in the inconvenience of not wearing corrective lenses for the initial few weeks. I'll look into the fasting and Gerson testimonials to see how they can be superimposed onto this line of though…

 
Last edited:

InChristAlone

Member
Joined
Sep 13, 2012
Messages
5,955
Location
USA
I'd like to see the testimonials as I myself have been trying to reverse myopia through decreasing lens strength. There are also websites that promote a kind of hormesis effect and getting stronger vision. If it is nutritional then you'd have to explain the many people without myopia yet eat terrible American diets. Also there is a difference between someone with low myopia and lens induced high myopia. Low myopia people can easily get back 20/20 vision if they spend lots of time outside little time indoors on computers. So testimonials of going on fasts and things like that... well what else were they doing? Were they at a retreat in the tropics? Getting lots of sunlight? Low myopia? Search on youtube, multiple people getting stronger and stronger vision without changing their diet, just by: 1. not looking at the computer with their full lens strength 2. giving breaks between computer work to look into the distance 3. Only wearing enough strength as they need which lets them do active focus

I'd be interested in people experimenting, but they also have to report their lens strength in the beginning and then at the end after doing a snellen chart test.
 
OP
Travis

Travis

Member
Joined
Jul 14, 2016
Messages
3,189
If it is nutritional then you'd have to explain the many people without myopia yet eat terrible American diets.
Quite impossible to do, since the word 'terrible' is not in the scientific vocabulary. You'd have to define such people as eating either unnatural amino acid ratios or hyperglycemic diets. Also, hormonal effects can be exerted independently of diet: The action of insulin can depend largely on the state of the pancreas, and the state of the pancreas can be independent of diet.
Low myopia people can easily get back 20/20 vision if they spend lots of time outside little time indoors on computers.
These are retinal effects. My understanding accounts for slight changes in the retinal microtubule structure in response to light—small translations or elongations in rod and cone cells bringing them coincident with the focal point of light. Explaining this is explaining microtubule and rhodopsin dynamics, something else entirely. The methylglyoxal adducts are necessary to explain the undeniable effects of glucose on visual acuity, on cataracts, and the experimentally determined variance in corneal refraction. Let me remind you that the other theories wouldn't even begin to explain this . . . unless one can think somehow that looking at a computer screen can effect osmosis.
 
Last edited:

InChristAlone

Member
Joined
Sep 13, 2012
Messages
5,955
Location
USA
What is a hyperglycemic diet? If it just based on glycemic index, then many Americans are getting hyperglycemic diets. Including me. I am not doubting your theory and that it does have an effect on myopia I am doubting the reversal aspect.
 

x-ray peat

Member
Joined
Dec 8, 2016
Messages
2,343
Myopia appears to me, at the moment, to be a difference in refractive index between the cornea and the lens‐(eye).

The cornea is a meniscus lens, and the lens‐(eye) is is a biconcave lens. The cornea is convergent; the lens‐(eye) is divergent. Myopia can either be caused by an increase in the refractive index of the cornea, or a decrease in the refractive index of the lens‐(eye). I think the former difference in refraction is, by far, the more common. It's hard to imagine many scenarios in which the lens would decrease in refractive index.

The cornea is made of collagen: Since aged collagen has a higher refractive index, it follows that naïve collagen would have a lower refractive index. This is more than intuitive; this can be inferred directly from experimental data. This leads to the idea that the refractive index of the cornea can be lowered by increasing the rate of collagen synthesis (perhaps through vitamin C and gelatin).

High blood glucose is expected to either increase the refractive index of the cornea or the lens‐(eye), individually or in tandem: causing either myopia, hyperopia, or no change depending on pharmacokinetics, insulin, and protein synthesis rates. Since the cornea is extracellular, I would expect the cornea to be more liable to the methylgloxal addition reactions consequent of high glucose. For this reason, anything with a high glycemic index should probably be avoided—there are also many other good reasons to avoid such foods.

Reversing myopia could be the Chinese diet in reverse: low glycemic foods with high lysine. The way I view it, myopia is a function of unnaturally‐high glycemic foods amplified by an unnatural dietary amino acid ratio. Not wearing corrective lenses while consuming fruit and collagen seems like it would be the best approach. If you would like to test this thought, perhaps check‐out testimonials of myopia reversals during fasting and Gerson retreats. I think you might find confirmation of this theory by doing so. I'm trying to legitimize all observations with a scientific model, and intend on doing so until it's either modified, falsified, or becomes undeniable Truth to others—the way I see it. Explanations involving rapid eyeball change—or in the depth of the optical cavity—sound absurd, and experimental observations directly contradict it. The osmotic theories are likewise absurd, as they cannot explain why the consumption the more osmotic salt (NaCl) does nothing. (Keep in mind that the osmotic theories were created to explain how sugar causes refractive changes in a time period completely oblivious to methylglyoxal–protein adducts.) I consider these explanations examples of 'lollipop science,' both for their absurdity and their inability to explain the data. In scientific articles about diabetes and refraction changes, you commonly find the word 'paradox'—a word which essentially can be seen as a tacit admission or an incorrect model.

I don't think my theory can be so easily falsified; it reflects the data near‐perfectly. (Optical equations are forthcoming.)

Since gelatin and fruit are Peat‐friendly, I can recommend them with complete impunity here.

I would think the hardest part about reversing myopia lies in the inconvenience of not wearing corrective lenses for the initial few weeks. I'll look into the fasting and Gerson testimonials to see how they can be superimposed onto this line of though…
Thanks Travis I did a quick search on gelatin and eye sight and found lots of anecdotal reports of eyesight improvements. I think I may get back on my morning gelatin and coffee.
 

Koveras

Member
Joined
Dec 17, 2015
Messages
720
IX. Metabolic Considerations

The sorbitol pathway of the lens has been thoroughly‐studied: Enzyme's have been analyzed; they have been homogenized and centrifuged, then precipitated and further refined through column chromatography. Two glycolytic enzymes found in the lens have been kinetically measured under a variety of substrates. These two enzymes, aldose reductase and polyol dehydrogenase, are dependent on their cofactor NADH. This means that either a paucity of niacin or a change in redox balance could theoretically change methylglyoxal concentrations, and subsequent changes in lens refractive index. Also, if present, glutathione working through glyoxylase I & II would be expected to play a role. Glutathione would be expected to lower methylglyoxal concentrations through the well‐characterized glyoxal cycle (see Thornally).

Good point. I just thought that I had to mention a Peat‐oriented food once in a while, so that I don't get lynched by the Peat‐mob.

Prostaglandins Leukot Essent Fatty Acids. 2017 Dec;127:20-24. doi: 10.1016/j.plefa.2017.10.004. Epub 2017 Oct 7.
Coconut phytocompounds inhibits polyol pathway enzymes: Implication in prevention of microvascular diabetic complications.
Sheela DL1, Nazeem PA2, Narayanankutty A2, Shylaja RM2, Davis SP2, James P2, Valsalan R2, Devassy Babu T2, Raghavamenon AC2.

Coconut oil (CO), the primary choice of cooking purposes in the south Asian countries, is rich in medium chain saturated fatty acids, especially lauric acid (50-52%). The oil has high medicinal use in Ayurvedic system and known to contain polyphenolic antioxidants. Studies have reported that CO improves insulin sensitivity and shows hypoglycemic effect. However, there is no information regarding its effect on chronic diabetic complications including retinopathy and nephropathy is available. The secondary diabetic complications are mediated by the activation of polyol pathway, where aldose reductase (AR) plays crucial role. In this study, in silico analysis has been used to screen the effect of CO as well as its constituents, MCFAs and phenolic compounds, for targeting the molecules in polyol pathway. The study revealed that lauric acid (LA) interacts with AR and DPP-IV of polyol pathway and inhibits the activity of these enzymes. Validation studies using animal models confirmed the inhibition of AR and SDH in wistar rats. Further, the LA dose dependently reduced the expression of AR in HCT-15 cells. Together, the study suggests the possible role of CO, particularly LA in reducing secondary diabetic complications.
 
OP
Travis

Travis

Member
Joined
Jul 14, 2016
Messages
3,189
Thanks Travis I did a quick search on gelatin and eye sight and found lots of anecdotal reports of eyesight improvements. I think I may get back on my morning gelatin and coffee.
Really. That's good to know, and I still really see myopia in protein chemistry terms and think that collagen turnover plays a role. I am working on the ray tracing model right now—taken from experimental measurements and represent accurate dimensions—but still need to work out some differential equations. The lens has a refractive index gradient, meaning that the refractive index increases from the centre outward. This is going to involve a three dimensional differential equation, as seen here: Sharma, Anurag. "Ray tracing in gradient-index lenses: computation of ray–surface intersection." Applied optics (1986)

The lens gradient serves to increase the refractive index, according to experimenters.

But I have done most of the work already; I have a program which accurately models an incoming parallel hollow cylinder of light through the cornea (but stopping at the lens). The radius of the cylinder can be adjusted; all variables are interlinked. This is already a great improvement of most illustrations since it follows Snell's Law and the geometry is taken from experimental data (a monkey).

ray.png ray1.png ray2.png ray3.png

As a divergent biconvex lens, I'm getting the impression that the light will emerge from the lens roughly parallel with optic axis.

I chose to use a cylinder of light since we see light coming straight at us. The rays commonly depicted in diagrams, at an extreme angle, represent peripheral rays that we never pay much attention to. Seen below is a characteristic depiction of such a ray trace:

light.png click to embiggen

This is far from accurate. Not only are light rays of this angle diffracted away from the retina, and not focused, this illustration perpetuates the myth that 'we see things upside down.'

light2.png click to embiggen

The one directly above is only slightly better: the rays it incorporates into the model are coming straight at the viewer. However, the one above also has a flaw: This model fails to account for the divergent nature of the lens, much less the gradient, and draws the rays as though not even there. I ask the model: 'Why then do we even have a lens at all?'

This model also perpetuates the myth that 'we see things upside down.'

I predict that incoming parallel rays will emerge parallel with the optical axis, will not cross or invert, and will be beamed straight towards the retina, through rhodopsin, down microtubules, and into the brain at speeds determined only by the Förster resonance energy transfer equation and not the clumsy, impossible, low‐fidelity, molecular mechanism currently purported as truth on media outlets such as wikipedia.org and most standard biochemistry textbooks.
 
Last edited:

noordinary

Member
Joined
Jun 1, 2016
Messages
209
@Travis found this, while researching different topic:
Tissue-Specific Actions of Glucocorticoids on Apoptosis: A Double-Edged Sword
"Other cell types in the nervous system that undergo apoptosis in response to glucocorticoids include cells of the eye. Prolonged or high doses of glucocorticoid treatment often can increase ocular pressure and changes in the trabecular meshwork cells (cells that drain the aqueous humor from the eye) that can lead to glaucoma [29]. Dexamethasone has been reported to induce apoptosis in bovine trabecular meshwork cells in culture, which may contribute to the progression of steroid-induced glaucoma [30]. Elevated doses of dexamethasone also induce apoptosis and necrosis in cultured bovine corneal epithelial cells [31] and cultured human corneal epithelial cells [32]. While the direct role of GC-induced apoptosis in the eye in vivo has yet to be elucidated, it is clear that critical eye cell types are sensitive to glucocorticoids."
29. Wordinger R.J., Clark A.F. Effects of glucocorticoids on the trabecular meshwork: Towards a better understanding of glaucoma. Prog. Retin. Eye Res. 1999;18:629–667. doi: 10.1016/S1350-9462(98)00035-4.
30. Gu Y., Zeng S., Qiu P., Peng D., Yan G. Apoptosis of bovine trabecular meshwork cells induced by dexamethasone. Zhonghua Yan Ke Za Zhi. 2002;38:302–304.
31. Chen W.L., Lin C.T., Yao C.C., Huang Y.H., Chou Y.B., Yin H.S., Hu F.R. In-vitro effects of dexamethasone on cellular proliferation, apoptosis, and Na+-K+-ATPase activity of bovine corneal endothelial cells. Ocul. Immunol. Inflamm. 2006;14:215–223. doi: 10.1080/09273940600732380.
32. Bourcier T., Forgez P., Borderie V., Scheer S., Rostene W., Laroche L. Regulation of human corneal epithelial cell proliferation and apoptosis by dexamethasone. Invest. Ophthalmol. Vis. Sci. 2000;41:4133–4141.
 
OP
Travis

Travis

Member
Joined
Jul 14, 2016
Messages
3,189
@Travis found this, while researching different topic:
Tissue-Specific Actions of Glucocorticoids on Apoptosis: A Double-Edged Sword
"Other cell types in the nervous system that undergo apoptosis in response to glucocorticoids include cells of the eye. Prolonged or high doses of glucocorticoid treatment often can increase ocular pressure and changes in the trabecular meshwork cells (cells that drain the aqueous humor from the eye) that can lead to glaucoma [29]. Dexamethasone has been reported to induce apoptosis in bovine trabecular meshwork cells in culture, which may contribute to the progression of steroid-induced glaucoma [30]. Elevated doses of dexamethasone also induce apoptosis and necrosis in cultured bovine corneal epithelial cells [31] and cultured human corneal epithelial cells [32]. While the direct role of GC-induced apoptosis in the eye in vivo has yet to be elucidated, it is clear that critical eye cell types are sensitive to glucocorticoids."
29. Wordinger R.J., Clark A.F. Effects of glucocorticoids on the trabecular meshwork: Towards a better understanding of glaucoma. Prog. Retin. Eye Res. 1999;18:629–667. doi: 10.1016/S1350-9462(98)00035-4.
30. Gu Y., Zeng S., Qiu P., Peng D., Yan G. Apoptosis of bovine trabecular meshwork cells induced by dexamethasone. Zhonghua Yan Ke Za Zhi. 2002;38:302–304.
31. Chen W.L., Lin C.T., Yao C.C., Huang Y.H., Chou Y.B., Yin H.S., Hu F.R. In-vitro effects of dexamethasone on cellular proliferation, apoptosis, and Na+-K+-ATPase activity of bovine corneal endothelial cells. Ocul. Immunol. Inflamm. 2006;14:215–223. doi: 10.1080/09273940600732380.
32. Bourcier T., Forgez P., Borderie V., Scheer S., Rostene W., Laroche L. Regulation of human corneal epithelial cell proliferation and apoptosis by dexamethasone. Invest. Ophthalmol. Vis. Sci. 2000;41:4133–4141.
Interesting article (reference №29). Not knowing any details, a person could be temped to think of this change in pressure as the result of dexamethasone working through the membrane mineralcorticoid receptor.⁽¹⁾ However! despite dexamethasone being capable of binding the mineralocorticoid receptor, it has a relatively high dissociation constant here leading to an unstable bond.⁽²⁾ So the effects of dexamethasone are most surely mediated through the glucocorticoid receptor by transcribing mRNA for extracellular proteins and enzymes. This has the effect of reducing pore size of the trabecular meshwork—the sluice gate of the eyball—thereby increasing intraocular pressure.

This could perhaps be another explanation of how sugar, diabetes, and insulin could be linked to myopia: the osmotic force theory resurrected, with cortisol. I can almost hear their proponents perking‐up, rallying, and preparing to cheer‐lead this finding—using it to bolster archaic osmotic beliefs. But would they have a point? Is myopia pre‐glaucoma or is it pre‐cataract? Or to state it another way: Is myopia caused by intraocular pressure? or is it caused by the methylglyoxal crosslinking of collagen?

The epidemiological data can help:

Mitchell, Paul. "The relationship between glaucoma and myopia: the Blue Mountains Eye Study." Ophthalmology (1999)

Brown, N. A. "Cataract: the relation between myopia and cataract morphology." British journal of ophthalmology (1987)

There is some indication that both glaucoma and cataract are associated with myopia:

'An association between myopia and primary open-angle glaucoma has been recognized for decades and documented in numerous case series and in most, but not all, case–control studies.' ―Mitchell

'The relationship of cataract to high (or degenerative) myopia is a well accepted concept.' ―Brown

Proponents of osmotic theory swell with pride at seeing risk ratios between two and three:

myopia.png click to embiggen: Prevalence of glaucoma and concomitant myopia.

They will enjoy a brief period of satisfaction, perhaps giving them a few minutes to imagine if adrenalectomies could prevent refractive changes in rabbits . . . until the doubts start to creep in. Take for instance the fact that myopia often occurs with no pressure changes at all, sugar consumption is much more related than salt consumption, and that Daubs found absolutely no association between the two in the United Kingdom.⁽³⁾ But what is especially troublesome for the osmotic crowd is the overwhelming evidence for methylglyoxal being the primary cause.

The prevalence ratios between myopia and cataracts greatly overshadows those found with glaucoma.

myopia2.png click to emgiggen: Prevalence of cataract and concomitant myopia.

And the overwhelming majority of people with cataracts have a positive refractive shift, or myopia; this is exactly what you'd expect through a ray tracing analysis using an increased corneal refractive index.

myopia.png click to embiggen: Graph depicting lens power change associated with cataract.

Cataract is undeniably caused by methylglyoxal adducts, sometimes called 'glycation' or 'maillard products.' Since myopia proceeds cataract, it could be seen as a pre‐cataract condition. Myopia is a few more crosslinks than normal—cataract yet even more crosslinks.

'In particular, it is shown that a marked myopic shift had occurred in the four years preceding the presentation of cataract only in those eyes with nuclear cataract.' ―Brown

Although the osmotic theory has received a temporary revival with @noordinary and the findings of increased ocular pressure caused by glucocorticoids—explaining the long‐linked association between myopia and blood sugar—it pales in comparison to the weight of evidence in support of the methylglyoxal theory.

[1] Wehling, M. "Membrane receptors for aldosterone: a novel pathway for mineralocorticoid action." American Journal of Physiology-Endocrinology And Metabolism (1992)
[2] Reul, Johannes. "The brain mineralocorticoid receptor: greedy for ligand, mysterious in function." European journal of pharmacology (2000)
[3] Daubs, J. G. "Effect of refractive error on the risk of ocular hypertension and open angle glaucoma." Transactions of the ophthalmological societies of the United Kingdom (1981)
 
Last edited:
OP
Travis

Travis

Member
Joined
Jul 14, 2016
Messages
3,189
But those certainly appear to be interesting and specific effects that dexamethasone and cortisol have on the trabecular meshwork—acting to increase intraocular pressure. Could this be an adaptive mechanism to either (1) offset the refractive index change consequent of increased glucose by inducing a change of equal and opposite magnitude, or (2) to prevent this refractive change by limiting the influx of glucose through the formation of a pressure gradient?
 
Last edited:

Amazoniac

Member
Joined
Sep 10, 2014
Messages
8,583
Location
Not Uganda
- How does spending time outdoors protect against myopia? A review
Abstract said:
Myopia is an increasingly common condition that is associated with significant costs to individuals and society. Moreover, myopia is associated with increased risk of glaucoma, retinal detachment and myopic maculopathy, which in turn can lead to blindness. It is now well established that spending more time outdoors during childhood lowers the risk of developing myopia and may delay progression of myopia. There has been great interest in further exploring this relationship and exploiting it as a public health intervention aimed at preventing myopia in children. However, spending more time outdoors can have detrimental effects, such as increased risk of melanoma, cataract and pterygium. Understanding how spending more time outdoors prevents myopia could advance development of more targeted interventions for myopia. We reviewed the evidence for and against eight facets of spending time outdoors that may protect against myopia: brighter light, reduced peripheral defocus, higher vitamin D levels, differing chromatic spectrum of light, higher physical activity, entrained circadian rhythms, less near work and greater high spatial frequency (SF) energies. There is solid evidence that exposure to brighter light can reduce risk of myopia. Peripheral defocus is able to regulate eye growth but whether spending time outdoors substantially changes peripheral defocus patterns and how this could affect myopia risk is unclear. Spectrum of light, circadian rhythms and SF characteristics are plausible factors, but there is a lack of solid evidence from human studies. Vitamin D, physical activity and near work appear unlikely to mediate the relationship between time spent outdoors and myopia.
 
Joined
Nov 18, 2018
Messages
765
@Diokine “I wear contact lenses close to -2.5, and I have experienced near perfect vision without lenses under the influence of dopamine agonists and altered states of mind.” Which dopamine agonist did you use?
 

Similar threads

Back
Top Bottom