Rationale of Basic and Cellular Mechanisms Considered in Updating the Staging System for Diabetic Retinal Disease

Area of Science:

• Ophthalmology and Vision Science
• Diabetology
• Cellular and Molecular Medicine

Background:

• Diabetic retinal disease (DRD) is a leading cause of vision loss in diabetic patients.
• Hyperglycemia is a primary driver of early DRD lesions.
• Current DRD staging systems require updates to incorporate fundamental biological mechanisms.

Purpose of the Study:

• To review preclinical and clinical evidence on basic and cellular mechanisms relevant to DRD.
• To identify potential targets for updating the DRD staging system.
• To inform future therapeutic interventions and treatment strategies for DRD.

Main Methods:

• A comprehensive review of preclinical and clinical evidence by the Basic and Cellular Mechanisms Working Group (BCM-WG).
• Classification of identified targets based on evidence grids, supporting evidence levels, and future relevance to DRD.
• Grouping of 40 identified targets into concepts or evaluating them as specific candidates.

Main Results:

• VEGFA, peroxisome proliferator-activated receptor-alpha pathways, plasma kallikrein, and angiopoietin 2 were identified as promising biomarkers.
• These biomarkers show potential for diagnostic, monitoring, predictive, prognostic, and pharmacodynamic applications in DRD.
• Key research concepts include inflammation, oxidative signaling, vasoprotection, neuroprotection, mitophagy, and nutrient/microbiome interactions, all regulated by hyperglycemia.

Conclusions:

• Several promising targets and cellular mechanisms were identified for potential inclusion in an updated DRD staging system.
• While immediate integration is limited, continued research into these targets is crucial.
• These efforts may lead to novel biomarkers and therapeutic targets, ultimately benefiting patients with diabetes.