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EDITORIAL
Year : 1997  |  Volume : 45  |  Issue : 1  |  Page : 5-6

Cataract - Where do we stand ?


Correspondence Address:
D Balasubramanian


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Source of Support: None, Conflict of Interest: None


PMID: 9475005

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How to cite this article:
Balasubramanian D. Cataract - Where do we stand ?. Indian J Ophthalmol 1997;45:5-6

How to cite this URL:
Balasubramanian D. Cataract - Where do we stand ?. Indian J Ophthalmol [serial online] 1997 [cited 2024 Mar 29];45:5-6. Available from: https://journals.lww.com/ijo/pages/default.aspx/text.asp?1997/45/1/5/15031

Cataract still reigns unabated as the major blinding disease around the world. It strikes the population of the tropical countries (which also happen to be by and large the economically less developed ones) earlier and in larger numbers than those in the countries of Europe, northern America or Down Under. The annual incidence of cataract in India is estimated to be four million. Of these, the number that get operated for better eye sight is only 2.5 million, leaving a backlog that accumulates yearly. Remarkable strategies have been adopted to handle this problem. The time-tested one is the organisation of rural eye camps where patients are collected in large numbers at a given spot and a team of eye care people examine them and do (largely intra-capsular) cataract surgery on them. The numbers handled are large - almost 300 people are treated per day and the success rate is not bad either - over 80%. Yet the backlog remains.

Despite these heroic efforts, complications and post-operative difficulties do arise. It is in order to solve these and also to handle the entire problem of rural eye care in a more comprehensive manner that the novel idea of Primary Eye care Centres (PECC) has come about. The pioneer in this idea is the L.V.Prasad Eye Institute (LVPEI), Hyderabad, India, which has already established several such PECCs in some districts in the state of Andhra Pradesh, India. Each such centre operates on the concept of "Eye care team". This including an ophthalmologist, two optometrists, some associate para-medical and administrative staff. The ultimate idea is for these centres to eventually cover the entire district and offer eye care including surgery of the type and sophistication that is comparable to those available anywhere.

There are several inherent advantages in this idea. The patient can return for further advice and treatment if necessary; and the PECCs are able to monitor the ocular health of the population in a continuing, sustained and effective fashion. Thus the system offers a very high level of success both healthwise and financially; also these district eye centres maintain an organic connection with the LVPEI professionally and educationally. This allows them to operate with a high degree of competence, confidence and connectivity with new developments. The level of participation from the population in such centres is high, leading to their acceptability, viability, growth and success. The experience of this handful of district eye care centres can be successfully cloned and multiplied to the 530 districts of India in a very short time; that would provide an eye care net that extends through the length and breadth of this sprawling nation.

The current estimates of the annual budget of one such PECC (performing 1500 surgeries with intraocular lens) is approximately Rs. l.5 million (US $0.05 million). The yearly cost for the nation in establishing 530 PECCs would thus be Rs.1 billion (US $25 million). Considering that the current estimates of cataract operation alone run to Rs. l.2 billion (US $36 millions) per year in India, the idea of district eye care centres that would cater to all eye diseases - trachoma, glaucoma, corneal infections and the rest - takes on a larger meaning in eye care and the slogan "Total Eye Care by the Next Millennium " is a reachable goal as well, at least by the year 2005.

The biological roots of the problem are yet to be nipped or clipped. Cataract, the major problem, has not waned but is on the increase. While there have been remarkable surgical advances in handling cataract, basic research into the factors, the aetiology, the treatment and prophylaxis have not been given us any important leads into containing this scourge. We need to put in efforts into basic research on cataract but we have not been able to identify one or a handful of approaches on which we should put in greater emphasis than others. Cataract is caused by just everything; the litany grows every year -ageing, genetics, diabetes, improper diet, increased sunlight, the ozone hole, smoking etc. There is no single solution, but the one staple theory that has been of some value is that of oxidative stress. Analysis of the results on studies on radiation-induced cataract, the sunlight-cataract connection, smoking-cataract connection or even senile cataract has shown one thing in common : oxidative stress increases while endogeneous anti-oxidant defence appears to be insufficient or reduced, leading to lens opacification. The suggestion offered by these studies is that increased uptake of anti-oxidants in the daily diet (or as supplements) would be beneficial in increasing the defence and hopefully in an attempt to postpone the onset of cataract (and several other diseases).

Having said this, when one looks for the presence of oxidized products in the cataractous lens, the results are not unequivocal. Our own researches show that the accumulation of coloured compounds or pigments in the ageing lens or in cataract is due to oxidative stress and that several of these pigments in turn act as pro-oxidants and increase the oxidative stress in the tissue. While this is very well, the identification of oxidized or oxidation-damaged proteins in the lens has not been easy. Analysis of the crystallins in the nuclei of normal and cataractous human lenses, done by Garland, Tabor-Duglas and Datiles of the NEI in the US, has produced the surprising result that there is very little really insoluble crystallins in the cataractous lens. (Most of the pigments that accumulate in the ageing and cataractous lenses are protein-bound, and are products of protein sidechain oxidation). Most of the water-insoluble material can be solubilized in a cocktail of urea, detergent and the thiol reagent DTT. Electrophoresis of the material shows no covalent cross-linking other than perhaps increased disulfides. The molecular weights and the isoelectric points of the proteins from cataractous lens nuclei are about the same as those from normal tissue. This means that large covalent (non-disulfide) polymeric aggregates of the lens proteins are not prevalent to significant extents in the clinical tissue, though we need to isolate and study the very small amounts in which they may occur, since these will contribute to light-scattering and compromised transparency. We also need to look at more lenses (particularly from the tropical regions) and in greater detail, perhaps with newer approaches.

Would the solubility of a protein become different even if its molecular integrity is not ? That appears a possibility in light of the realization that conformational changes that can lead to aggregation and plaque formation in proteins. A protein that is misfolded can self-aggregate and precipitate. This indeed has been the basis of our understanding of prion diseases such as bovine spongiform encelopathy (BSE) or what is called the mad cow diseases, and similar ailments involving amyloid plaques such as Alzheimer disease. P. Frederikse and J. Piatigorsky, also of NEI, looked into this aspect of protein aggregation linked to oxidative stress and considered the possibility that cataract may in part be an amyloidogenic disease just as Alzheimer senile dementia is. When they looked for the precursor protein and the amyloid plaques in adult monkey lenses that were put under oxidative stress (peroxide or UV radiation), they could detect these as proliferative responses to the assault. This new line needs to be pursued further. One would, of course, then look for agents that would restore the appropriate confirmation and refold proteins into their correct shape thereby preventing precipitating and plaque formation.

Historically, this idea was triggered by the remarkable suggestion made by Horwitz of the Jules Stein Eye Institute at UCLA in 1992 that the alpha-crystallin of the lens cortex might itself act as such a "chaperone " molecule which would help in the right folding and solubilising of other proteins in the lens. That this molecule may indeed serve the chaperone function, and the conditions under which such chaperoning happens, has been studied in greater detail and effectively by Mohan Rao of CCMB, Hyderabad, India. This then gives the opportunity to look for drugs or small molecules (e.g. pantothene?) that would enhance or promote the chaperone activity of alpha-crystallin; work has already been started in this area by Mohan Rao and by Clark of Seattle, in the US.

Finally, there is the intriguing possibility that cataract can be an auto-immune phenomenon. Work by Shinohara, R Chylack and others from Boston shows that there are detectable levels of anti-lens antibodies in the serum of cataract patients. These antibodies are against lens antigens, notably the crystallins (in particular some of the beta-crystallins). Some of these antigen sequences appear related to some microbial toxin epitopes, explaining perhaps why the antibodies were also seen to be cytotoxic. Sera from cataract patients were able to kill mouse and human lens epithelial cells in culture, but the sera from non-cataract individuals did not. So, is there an auto-immune aspect to cataract?

Clearly these are new approaches. Some of them are perhaps in tune with what is more fashionable in modern biology, while others are more far-reaching and fundamental. We are also moving from the strictly molecular to the cell biological approaches to understanding cataract. Breakthroughs are not to be expected in the current year but there is no telling when a very important new approach might emerge. Knowing the pace and ferment of modern biology, it would be no surprise if such a new approach were to come within the next couple of years.




 

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