INTRAOCULAR GENE-TRANSFER OF CILIARY NEUROTROPHIC FACTOR PREVENTS DEATH AND INCREASES RESPONSIVENESS OF ROD PHOTORECEPTORS IN THE RETINAL DEGENERATION SLOW MOUSE

Several mutations causing both photoreceptor degeneration and malfunct ion have been identified in humans and animals. Although intraocular i njection of trophic factors has been shown to reduce photoreceptor dea th in a few conditions of rapid photoreceptor loss, it is unclear whet her long-term beneficial changes in functional properties of affected photoreceptors can be obtained by treatment with these factors. The rd s/rds mouse is a spontaneous mutant bearing a null mutation in the rds /peripherin gene, which is linked to many forms of dominant retinal de generations in humans. Here, we report that intraocular adenovirus-med iated gene transfer of ciliary neurotrophic factor (CNTF) in this muta nt reduces photoreceptor loss, causes a significant increase in the le ngth of photoreceptor segments, and results in a redistribution and an increase in the retinal content of the photopigment rhodopsin. These effects are accompanied by a significant increase in the amplitude of the a- and b-waves of the scotopic electroretinogram. These results su ggest that continuous administration of CNTF could potentially be usef ul for the treatment of some forms of retinal degeneration.