Repeated injections of a ciliary neurotrophic factor analogue leading to long-term photoreceptor survival in hereditary retinal degeneration

PURPOSE. To determine whether ciliary neurotrophic factor (CNTF) or brain-d erived neurotrophic factor (BDNF) treatment leads to long-term photorecepto r survival in hereditary retinal degeneration. METHODS. hn autosomal dominant feline model of rod-cone dystrophy was used throughout the study with two normal animals. In the first experiment, intr avitreal injections of a human CNTF analogue (Axokine; Regeneron Pharmaceut icals, Tarry-town, NY) were administered to one eye of each animal (n = 10) beginning on postnatal day 10 and were repeated every 4 weeks. Clinical an d histopathologic examinations were performed at 5.5, 9.5, and 13.5 weeks. In the second experiment, animals (n = 17) were randomly assigned to receiv e intravitreal injections of either Axokine (at half the initial dose), hum an BDNF, or the vehicle for Axokine to one eye at 5.5 weeks. The same thera py was repeated every 4 weeks in each group. Clinical and histopathologic e xaminations were performed at 9.5, 13.5, and 17.5 weeks. Photoreceptor surv ival was assessed by cell counting. Apoptotic cells were identified by morp hology and a modified TdT-dUTP terminal nick-end labeling (TUNEL) technique . In the third experiment, two normal animals were treated with Axokine as in the first experiment. Glial fibrillary acidic protein (GFAP) immunohisto chemistry was performed to assess glial cell reaction. RESULTS. In the first two experiments, Axokine significantly prolonged phot oreceptor survival (P < 0.01) and reduced the presence of apoptotic cells ( P < 0.05) and TUNEL-positive cells (P < 0.05). In the second experiment, re sults in the the BDNF- and sham-injected eyes were not significantly differ ent from those in the untreated eyes. Minimal posterior subcapsular catarac t and mild retinal folds were found in all Axokine-treated eyes in both dys trophic and normal animals. These complications were milder in the second e xperiment when injections were started later and at a reduced dose. GFAP im munolabeling was also increased in all Axokine-treated eyes. CONCLUSIONS. Axokine, but not BDNF, delays photoreceptor loss in this hered itary retinal degeneration. Repeated injections maintain the protective eff ect.