Sunday, December 2, 2007

2.2.2 "Senile" cataracts

The term "senile cataract" has been banished from the lexicon of eye diseases, for PC reasons. Now it is "age-related cataract" and it still affects people over 60.

The lens nucleus would have received a lifetime of "insults" from various sources collectively known as the aging process. And from time to time, someone will report the discovery of a gene that can be turned on or off to alter the aging of, e.g., skin cells. Since lens fibers in the nucleus and deep cortex do not have any DNAs, so there is no such control. Cataracts, i.e., lens opacities, are seen primarily in the nucleus and the cortex, so it is a one-way aging street.

In the diagram above, opacities are shown in gray (and left=anterior and right=posterior of the lens; the posterior surface is more curved than the anterior). They are usually denoted as nuclear, supranuclear (lamellar), cortical, subcapsular (both anterior and posterior), and anterior polar (including pyramidal) cataracts. The last group is seen mostly in the pediatric population.

Age-related cataracts are predominantly nuclear with yellow to brown to black pigmentation and are frequently associated with other types of cataracts. The image below is a left eye with combination nuclear (the yellowish center) and cortical (the whitish off-center spokes) cataracts:

(courtesy of NEI/NIH)
Vision tends to vary with the extent of opacification. Typically, surgery is contemplated if the best correctable visual acuity is worse than 20/40. And the refractive error does change. Pure nuclear cataracts will require more minus power because of increasing myopia. In dense nuclear cataracts, the doctor cannot see in and the patient cannot see out. Surgery is the only recourse.

Now, we'll backup a little and examine what lens opacification really means and what leads up to it. Lens cells contain a large concentration of structural proteins known as the crystallins. In decreasing order of the molecular weight, we have the alpha-, beta-, and gamma-crystallins. Opacities are seen when these proteins aggregate and scatter light. It is much like the egg white going from clear to opaque when boiled - because of protein aggregation from heat denaturation. In the lens, it is the formation of disulfide bonds between cysteine moieties. The causative factor is therefore oxidation. In fact, the aging process has now been re-defined as that of oxidative stress - from, e.g., oxygen free-radicals. Indeed, when you are X-rayed, your body is actually oxidized in the macro sense. In the lens, the source of oxidation appears to be H2O2 in the aqueous humor and lipid hydroperoxides in the cells. (Some reported presence of superoxide dismutase in the lens that can remove the highly toxic superoxide.) Normally these compounds are removed by catalase and glutathione peroxidase; however, if these enzymes become inefficient for some reason (e.g., the peroxides are in overwhelming concentrations), then the sulfhydryl groups in the crystallins form disulfide bonds and the proteins aggregate.

The question of whether molecular chaperons, a role for alpha-crystallins, have failed to oversee protein unfolding and proper folding and re-folding has not met with definitive conclusion.

So, it would appear that by avoiding oxidation, one can escape from not only cataracts but also other tissue injuries. Of course that is not entirely possible. The alternative may indeed be ingestion of anti-oxidants that truly work. The question is which ones? There have been some retrospective epidemiological studies linking some vitamins and lower cataract incidences; however, large-scale clinical trials are yet to be done.

Medical therapy is not possible at present, it'll be like un-boiling the egg. In fact, if you can turn a hard-boiled egg back to its original form, then you'll have the first step towards cataract reversal. If then, you can also revive the cells, very quickly, you'd become wealthy beyond imagination, in more ways than one.


Anonymous said...

Unboiling an egg has been achieved:

What does this mean for cataracts?

EyeDoc said...

If protein aggregates can be unfolded and re-folded in situ, then yes, finally one step closer to a cure for cataracts.