Susceptibility to TGFb2-Induced Cataract Increases with Aging in the Rat

PURPOSE. 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)-b 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 TGFb-induced cataract. METHODS. Lenses from weanling, adult, and senile rats were cultured in defined serum-free medium with a range of concentrations of TGFb2. 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 TGFb. This included opacification, the formation of anterior subcapsular plaques, and accumulation of type I collagen and a-smooth muscle actin. Lenses from adult and senile animals, however, were generally more adversely affected by TGFb than lenses from weanlings. This study also showed that a low dose of TGFb administered over a prolonged period had an effect similar to that of a higher dose administered over a shorter period. CONCLUSIONS. An elevation of TGFb activity, either acute or chronic, and/or an age-related increase in lens cell susceptibility to TGFb may be triggering factors in the etiology of certain forms of cataract. (Invest Ophthalmol Vis Sci. 2000;41:3544 -3551)