Cellular and Molecular Mechanisms of Neuronal Degeneration in Early-Stage Diabetic Retinopathy

Title:Cellular and Molecular Mechanisms of Neuronal Degeneration in Early-Stage Diabetic Retinopathy

Volume: 22 Issue: 5

Author(s): Andrew Callan, Sonal Jha, Laura Valdez and Andrew Tsin*

Affiliation:

• Department of Neuroscience, School of Medicine, University of Texas Rio Grande Valley, USA

Abstract:

Background: Studies on the early retinal changes in Diabetic Retinopathy (DR) have demonstrated that neurodegeneration precedes vascular abnormalities like microaneurysms or intraretinal hemorrhages. Therefore, there is a growing field of study to analyze the cellular and molecular pathways involved to allow for the development of novel therapeutics to prevent the onset or delay the progression of DR.

Molecular Mechanisms: Oxidative stress and mitochondrial dysfunction contribute to neurodegeneration through pathways involving polyol, hexosamine, advanced glycation end products, and protein kinase C. Potential interventions targeting these pathways include aldose reductase inhibitors and protein kinase C inhibitors. Neurotrophic factor imbalances, notably brain-derived neurotrophic factor and nerve growth factor, also play a role in early neurodegeneration, and supplementation of these neurotrophic factors show promise in mitigating neurodegeneration.

Cellular Mechanisms: Major cellular mechanisms of neurodegeneration include caspase-mediated apoptosis, glial cell reactivity, and glutamate excitotoxicity. Therefore, inhibitors of these pathways are potential therapeutic avenues.

Vascular Component: The nitric oxide pathway, critical for neurovascular coupling, is disrupted in DR due to increased reactive oxygen species. Vascular Endothelial Growth Factor (VEGF), a long-known angiogenic factor, has demonstrated both damaging and neuroprotective effects, prompting a careful consideration of long-term anti-VEGF therapy.

Conclusion: Current DR treatments primarily address vascular symptoms but fall short of preventing or halting the disease. Insights into the mechanisms of retinal neurodegeneration in the setting of diabetes mellitus not only enhance our understanding of DR but also pave the way for future therapeutic interventions aimed at preventing disease progression and preserving vision.

Cite this article as:

Callan Andrew, Jha Sonal, Valdez Laura and Tsin Andrew*, Cellular and Molecular Mechanisms of Neuronal Degeneration in Early-Stage Diabetic Retinopathy, Current Vascular Pharmacology 2024; 22 (5) . https://dx.doi.org/10.2174/0115701611272737240426050930