# Exerkines in diabetic retinopathy: from mechanisms to therapeutic prospects

## TL;DR

This review explores how exercise-related factors called exerkines may help treat diabetic retinopathy by protecting the retina through various biological pathways.

## Contribution

The paper systematically maps exerkines to retinal cell types and evaluates their potential as therapeutic mediators in diabetic retinopathy.

## Key findings

- Exerkines like irisin and adiponectin influence retinal endothelial cells and microglia in diabetic retinopathy.
- Exercise modality-specific exerkine signatures suggest tailored therapeutic approaches for DR stages.
- Exerkines show potential as biomarkers and mediators of exercise-induced retinal protection beyond metabolic effects.

## Abstract

Diabetic retinopathy (DR) is a leading cause of vision loss worldwide, driven by chronic metabolic dysregulation that promotes inflammation, oxidative stress, and progressive neurovascular unit dysfunction in the retina. While regular exercise is an effective non-pharmacological strategy to reduce diabetes-related complications, accumulating evidence suggests that its retinal benefits extend beyond systemic metabolic control and are mediated in part by exercise-induced bioactive factors known as exerkines. Secreted from skeletal muscle, adipose tissue, liver, and other organs, exerkines act as endocrine signals linking physical activity to tissue-specific adaptations. This review provides a retina-focused, cell-type-oriented synthesis of current evidence implicating key exercise-responsive exerkines, including irisin, adiponectin, brain-derived neurotrophic factor, fibroblast growth factor-21, apelin, and clusterin, in pathways relevant to DR pathogenesis. We systematically map reported exerkine actions to retinal endothelial cells, pericytes, Müller glia, microglia, neurons, and the retinal pigment epithelium, while explicitly distinguishing findings from retinal or DR-specific models from those extrapolated from extra-ocular systems. We further integrate emerging data on exercise modality-specific exerkine signatures and discuss their translational relevance, limitations, and safety considerations across different stages of DR. In total, this review highlights exerkines as candidate mediators and biomarkers of exercise-retina crosstalk and outlines priorities for mechanistic validation and clinical translation alongside established therapies such as anti-VEGF treatment.