MODULATING RADIATION CATARACTOGENESIS BY HORMONALLY MANIPULATING LENTICULAR GROWTH-KINETICS

There is considerable evidence that the lens epithelium is the primary site of injury Leading to the development of cataracts following radi ation exposure. That the damaged cells of the epithelium are the proge nitors of the aberrantly differentiating fibers associated with the ca taract is indisputable. So too is the observation that post-radiation proliferative activity in the lens epithelium is required for cataract s to develop. The natural hormonal regulation of lens epithelial mitot ic activity in the frog offers the opportunity to alter the cell cycle of the lens epithelium in vivo, thus enabling the direct examination of the role of lenticular mitosis in the cytopathomechanism of radiati on-induced cataracts. The cell cycle of the lens epithelium of norther n leopard frogs was manipulated by hypophysectomy (to halt mitotic act ivity) and pituitary hormone administration (to stimulate baseline mit osis and reverse hypophysectomy-induced mitotic suppression). Animals were hypophysectomized, irradiated and injected with pituitary hormone replacement. Irradiated animals, irradiated animals + hormone replace ment and irradiated hypophysectomized animals served as controls. Cata ract development was evaluated by slit-lamp biomicroscopy and correlat ed with histologic determinations of mitotic index and meridional row disorganization on lens epithelial whole mounts. In another study, hyp ophysectomized-irradiated animals received varying concentrations of r eplacement hormone in an attempt to quantitatively modulate lens epith elial mitotic activity and determine the effect on cataractogenesis. I t was found that irradiated-hypophysectomized (mitosis halted) frogs f ailed to develop opacities, while those with hormonal replacement (mit osis reinstated) developed cataracts. Furthermore, in all instances. t he times of cataract onset and rates of progression directly correlate d with the mitotic activity in the lens epithelia. Finally, we were ab le to titrate lens epithelial mitotic activity, and later cataractogen esis, by administering varying concentrations of replacement pituitary hormone, resulting in concentration-dependent correlation between mit otic index and the onset and rate of lens opacification. The ability t o modulate cataractogenesis by way of altering cell proliferation is s trong evidence that the post-radiation growth fraction plays a central role in the cytopathomechanism of radiocataracts.