Therapeutic targeting of diabetic retinal neuropathy as a strategy in preventing diabetic retinopathy

Diabetes causes a panretinal neurodegeneration herein termed diabetic retinal neuropathy, which manifests in the retina early and progresses throughout the disease. Clinical manifestations include changes in the ERG, perimetry, dark adaptation, contrast sensitivity and colour vision which correlate with laboratory findings of thinning of the retinal neuronal layers, increased apoptosis in neurons and activation of glial cells. Possible mechanisms include oxidative stress, neuronal AGE accumulation, altered balance of neurotrophic factors and loss of mitohormesis. Retinal neural damage precedes and is a biologically plausible cause of retinal vasculopathy later in diabetes, and this review suggests that strategies to target it directly could prevent diabetes induced blindness. The efficacy of fenofibrate in reducing retinopathy progression provides a possible proof of concept for this approach. Strategies which may target diabetic retinal neuropathy include reducing retinal metabolic demand, improving mitochondrial function with AMPK and Sirt1 activators or providing neurotrophic support with neurotrophic supplementation.