Intravitreous Delivery of the Corticosteroid Fluocinolone Acetonide Attenuates Retinal Degeneration in S334ter-4 Rats

PURPOSE. To study the neuroprotective properties of low-dose, sustained-release intravitreous fluocinolone acetonide (FA) in transgenic S334ter-4 rats. METHODS. S334ter-4 rats aged 4 weeks were divided into four groups: 0.5 mu g/d FA-loaded intravitreous drug delivery implant (IDDI); 0.2 mu g/d FA-loaded IDDI; inactive IDDI; and unoperated controls. Electroretinography (ERG) was performed before surgery and every 2 weeks after surgery for 8 weeks. When the rats were 12 weeks of age, outer nuclear layer (ONL) and inner nuclear layer (INL) thicknesses were measured. Microglial cell counts were obtained from retinal wholemounts labeled for Iba-1. RESULTS. At the end of the study, unoperated and inactive IDDI-implanted rats demonstrated 50% to 60% reductions in ERG amplitudes compared with those recorded at 4 weeks (P < 0.001 for both groups). FA 0.2-mu g/d animals demonstrated 15% amplitude attenuation, while FA 0.5-mu g/d animals showed 30% reduction. ONL thickness in FA 0.2-mu g/d-treated eyes was 25.8% +/- 2.3% higher than in control group eyes (P < 0.001) and 30.0% +/- 2.1% higher than in inactive IDDI-implanted eyes (P < 0.001). In FA 0.5-mu g/d-treated eyes, ONL thickness was 22.4% +/- 2.8% higher than in control group eyes (P < 0.001) and 22.3% +/- 3.7% higher than in inactive IDDI-implanted eyes (P < 0.01). No statistically significant difference was observed between the two control groups. No statistically significant difference between the two FA-treated groups was found. FA-treated groups demonstrated significantly fewer activated microglial cells than control groups. CONCLUSIONS. Chronic intravitreous infusion of FA preserves ONL cell morphology and ERG a- and b-wave amplitudes and reduces retinal neuroinflammation in S334ter rats. Based on these findings, the synthetic corticosteroid FA may promise a therapeutic role in patients with retinal degeneration. (Invest Ophthalmol Vis Sci. 2010; 51: 4243-4252) DOI:10.1167/iovs.09-4492