Pathogenesis of neuronal cell death in diabetic retinopathy

    Diabetic retinopathy is a major complication in diabetic patients that can lead to vision loss worldwide. However, the precise mechanisms leading to the progression of diabetic retinopathy remained undetermined. Recent studies have indicated that neuronal abnormalities including retinal ganglion cell (RGC) neuropathy as well as vascular abnormalities are associated with the pathogenesis of diabetic retinopathy. Because neuronal cell death directly affect the visual functions of diabetic patients, ophthalmologists should consider both vascular and neuronal abnormalities in considering the pathogenesis of diabetic retinopathy.

    To elucidate the mechanisms of RGC neuropathy in diabetic retinopathy, we have used three-dimensional collagen gel retinal culture system. Under diabetic stress, mitochondria- and caspase-dependent cell death pathways are associated with neuronal cell death in diabetic retinas. Furthermore, the human retinal studies indicate that mitochondria- and caspase-dependent cell death pathways are activated in degenerative neurons in retinas of diabetic patients. These results indicate that the neuronal cell death pathways in cultured retinas are, in part, common with that in human retinas of diabetic patients.