PROTECTION OF MOUSE PHOTORECEPTORS BY SURVIVAL FACTORS IN RETINAL DEGENERATIONS

PURPOSE. To examine the protective effect of a number of survival fact ors on degenerating photoreceptors in mutant mice with naturally occur ring inherited retinal degenerations, including retinal degeneration ( rd/rd), retinal degeneration slow (rds/rds), nervous (nr/nr), and Purk inje cell degeneration (pcd/pcd), in three different forms of mutant r hodopsin transgenic mice and in light damage in albino mice. METHODS. Various survival factors were injected intravitreally into one eye of mice at or soon after the beginning of photoreceptor degeneration, wit h the opposite eve serving as the control, and the eves were examined histologically at later ages. The survival factors included brain-deri ved neurotrophic factor (BDNF), neurotrophin-3, neurotrophin-4, ciliar y neurotrophic factor (CNTF), Axokine(TM) (a mutein of CNTF), leukemia inhibitory factor, basic fibroblast growth factor, and nerve growth f actor and insulin-like growth factor II, either alone or in various co mbinations. RESULTS. Photoreceptor degeneration was slowed in rd/rd an d nr/nr mutant mice and in Q344ter mutant rhodopsin mice by certain fo rms of CNTF; the degeneration in Q344ter mice was slowed by Axokine an d by leukemia inhibitory factor; and the degeneration in a few nr/nr m ice was slowed by BDNF. The other agents were ineffective in these mic e, and none of the agents were effective in the other mutants and othe r mutant rhodopsin transgenic mice. However, light damage experiments that compared agent effectiveness in albino mice versus rats suggested a significant delivery problem with the very small mouse eye, thereby making the interpretation of negative findings equivocal in mutant mi ce. Basic fibroblast growth factor failed to protect tile mouse retina from the damaging effects of constant light, whereas it showed a stro ng protective effect in the rat, indicating an important species diffe rence. CONCLUSIONS. The slowing of degeneration in the rd/rd and Q344t er mutant mice demonstrated that intraocularly injected survival facto rs can protect photoreceptors from degenerating in animal models with tile same or similar genetic defects as those in human inherited retin al degenerations.