Neurodegeneration in diabetic retinopathy: Potential for novel therapies

The complex pathology of diabetic retinopathy (DR) affects both vascular and neural tissue. The characteristics of neurodegeneration are well-described in animal models but have more recently been confirmed in the clinical setting, mostly by using non-invasive imaging approaches such as spectral domain optical coherence tomography (SD-OCT). The most frequent observations report loss of tissue in the nerve fiber layer and inner plexiform layer, confirming earlier findings from animal models. In several cases the reduction in inner retinal layers is reported in patients with little evidence of vascular lesions or macular edema, suggesting that degenerative loss of neural tissue in the inner retina can occur after relatively short durations of diabetes. Animal studies also suggest that neurodegeneration leading to retinal thinning is not limited to cell death and tissue loss but also includes changes in neuronal morphology, reduced synaptic protein expression and alterations in neurotransmission, including changes in expression of neurotransmitter receptors as well as neurotransmitter release, reuptake and metabolism. The concept of neurodegeneration as an early component of DR introduces the possibility to explore alternative therapies to prevent the onset of vision loss, including neuroprotective therapies and drugs targeting individual neurotransmitter systems, as well as more general neuroprotective approaches to preserve the integrity of the neural retina. In this review we consider some of the evidence for progressive retinal neurodegeneration in diabetes, and explore potential neuroprotective therapies.