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 radiation exposure. That the damaged cells of the epithelium are the progenitors of the aberrantly differentiating fibers associated with the cataract is indisputable. So too is the observation that post-radiation proliferative activity in the lens epithelium is required for cataracts to develop. The natural hormonal regulation of lens epithelial mitotic 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 radiation-induced cataracts. The cell cycle of the lens epithelium of northern leopard frogs was manipulated by hypophysectomy (to halt mitotic activity) and pituitary hormone administration (to stimulate baseline mitosis and reverse hypophysectomy-induced mitotic suppression). Animals were hypophysectomized, irradiated and injected with pituitary hormone replacement. Irradiated animals, irradiated animals + hormone replacement and irradiated hypophysectomized animals served as controls. Cataract development was evaluated by slit-lamp biomicroscopy and correlated with histologic determinations of mitotic index and meridional row disorganization on lens epithelial whole mounts. In another study, hypophysectomized-irradiated animals received varying concentrations of replacement hormone in an attempt to quantitatively modulate lens epithelial mitotic activity and determine the effect on cataractogenesis. It was found that irradiated-hypophysectomized (mitosis halted) frogs failed to develop opacities, while those with hormonal replacement (mitosis reinstated) developed cataracts.(ABSTRACT TRUNCATED AT 250 WORDS)
Holsclaw
D S
DS
Department of Ophthalmology, University of California, San Francisco.
Rothstein
H
H
Medvedovsky
C
C
Worgul
B V
BV
D000818:Animals; D002386:Cataract / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D007016:Hypophysectomy; D007903:Lens Capsule, Crystalline / Q000166:cytology / Q000528:radiation effects*; D008938:Mitosis / Q000187:drug effects; D008940:Mitotic Index; D010908:Pituitary Hormones, Anterior / Q000494:pharmacology; D011894:Rana pipiens; D013997:Time Factors
D010908:Pituitary Hormones, Anterior