Proapoptotic and survival signaling in the neuroretina at early stages of diabetic retinopathy

PURPOSE Diabetic retinopathy (DR) has been classically considered a microcirculatory disease of the retina. However, before any microcirculatory abnormalities can be detected in ophthalmoscopic examination, retinal neurodegeneration is already present. The aim of the study was to analyze proapoptotic and survival signaling in the neuroretinas of diabetic patients at early stages of DR. METHODS The retinas from five diabetic donors at early stages of DR were compared with the retinas from five nondiabetic donors matched by age. Glial activation was evaluated by assessing glial fibrillar acidic protein (GFAP) with western blot and immunofluorescence. Proapoptotic molecules (FasL, procaspase-8, active caspase-8, total Bid, truncated Bid, Bim, and active caspase-3), as well as antiapoptotic markers (FLIP, BclxL, and cyclooxygenase-2 [COX-2]) were assessed with western blot. RESULTS GFAP and proapoptotic molecules (FasL, active caspase-8, truncated Bid (t-Bid), Bim, and active caspase-3) were significantly increased in the neuroretinas from diabetic patients compared to the control neuroretinas. In contrast, no significant differences in the expression of the antiapoptotic markers were found. CONCLUSIONS An imbalance between proapoptotic and survival signaling was found in diabetic neuroretinas. Our results reveal key mechanistic pathways involved in the neurodegenerative process that occurs in the early stages of DR.