Susceptibility to TGFbeta2-induced cataract increases with aging in the rat.
OBJECTIVE
Cataract is the most common cause of blindness in the world today, and yet there is no generally accepted treatment other than surgical intervention. Studies in rodent models designed to increase understanding of the molecular basis of cataract have shown that transforming growth factor (TGF)-beta induces morphologic and molecular changes similar to those associated with some forms of human cataract. Because aging is the most widely recognized risk factor for cataract, it is important that any animal model be examined in this context. This was a study of the effects of aging on susceptibility to TGFbeta-induced cataract.


METHODS
Lenses from weanling, adult, and senile rats were cultured in defined serum-free medium with a range of concentrations of TGFbeta2. The lenses were cultured for up to 7 days, photographed daily, fixed, and prepared for histology and immunolocalization. Opacification was quantified by image analysis.


RESULTS
Lenses from weanling, adult, and senile rats all underwent similar cataractous changes when exposed to TGFbeta. This included opacification, the formation of anterior subcapsular plaques, and accumulation of type I collagen and alpha-smooth muscle actin. Lenses from adult and senile animals, however, were generally more adversely affected by TGFbeta than lenses from weanlings. This study also showed that a low dose of TGFbeta administered over a prolonged period had an effect similar to that of a higher dose administered over a shorter period.


CONCLUSIONS
An elevation of TGFbeta activity, either acute or chronic, and/or an age-related increase in lens cell susceptibility to TGFbeta may be triggering factors in the etiology of certain forms of cataract.
Hales
A M
AM
Department of Anatomy and Histology and the Institute for Biomedical Research, The University of Sydney, New South Wales, Australia.
Chamberlain
C G
CG
McAvoy
J W
JW
D000199:Actins / Q000378:metabolism; D000375:Aging; D000818:Animals; D002386:Cataract / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D004198:Disease Susceptibility; D004305:Dose-Response Relationship, Drug; D005260:Female; D007908:Lens, Crystalline / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D000199:Actins; D016212:Transforming Growth Factor beta; D003094:Collagen