Interleukin-6 as a photoreceptor neuroprotectant in an experimental model of retinal detachment

PURPOSE. To test the hypothesis that interleukin (IL)- 6 prevents photoreceptor cell death during periods of retinal separation from the retinal pigment epithelium (RPE). METHODS. Retinal - RPE separation was created in wild-type C57BL mice, IL-6(-/-) mice, and Brown Norway rats by subretinal injection of 1% hyaluronic acid. In some animals, anti - IL-6 neutralizing antibody ( NAB) or exogenous IL-6 was administered into the subretinal space at the time of separation or at specified times afterward. Terminal deoxynucleotidyl transferase dUTP nick-end labeling ( TUNEL) was performed 3 days after separation to detect apoptotic photoreceptors. Photoreceptor cell counts were performed after 1 and 2 months. RESULTS. Loss of IL-6 function through genetic ablation ( IL-6 (-/-) mice) or injection of anti - IL-6 NAB resulted in significantly increased levels of TUNEL-positive staining 3 days after retinal RPE separation. One month after separation, outer nuclear layer (ONL) cell counts were significantly lower in IL-6 (-/-) mice or in animals injected with anti - IL-6 NAB than in controls. Gain of IL-6 function through the addition of exogenous IL-6 resulted in significantly increased ONL counts at 1 month but not at 2 months. Reinjection of IL-6 at 1 month led to continued preservation of ONL counts compared with controls. A window of opportunity for treatment was detected because delaying injection of exogenous IL-6 to 2 weeks after retinal RPE separation still resulted in significantly greater ONL cell counts compared with controls. CONCLUSIONS. IL-6 may serve as a photoreceptor neuroprotectant in the setting of retinal - RPE separation.