GLP-1 Treatment Improves Diabetic Retinopathy by Alleviating Autophagy through GLP-1R-ERK1/2-HDAC6 Signaling Pathway.

Area of Science:

• Ophthalmology
• Endocrinology
• Cell Biology

Background:

• Diabetic retinopathy (DR) pathogenesis involves oxidative stress, apoptosis, and excessive autophagy in retinal cells.
• Overstimulated autophagy accelerates DR progression, highlighting the need for therapeutic interventions.

Purpose of the Study:

• To investigate the protective effects of Glucagon-like peptide-1 (GLP-1) on retinal cells in type 2 diabetic rats.
• To elucidate the underlying mechanism of GLP-1's protective action against diabetic retinopathy.

Main Methods:

• Type 2 diabetes was induced in rats using a high-sugar, high-fat diet and streptozotocin.
• GLP-1 treatment was administered for one week post-diabetes onset.
• Key molecular markers including oxidative stress enzymes, GLP-1R, apoptosis-related genes, and autophagy markers were analyzed using Western blotting and immunohistochemistry.

Main Results:

• GLP-1 treatment reduced oxidative stress markers (NOX3, SOD2) and key autophagy marker LC3B in diabetic rats.
• GLP-1 increased the anti-apoptotic BCL2 expression and decreased caspase-3 levels.
• Treatment restored GLP-1 receptor (GLP-1R) expression and modulated signaling pathways (AKT, ERK1/2, HDAC6).

Conclusions:

• GLP-1 treatment effectively alleviates oxidative stress-induced autophagy and apoptosis in diabetic retinopathy.
• The protective mechanism involves the GLP-1R-ERK1/2-HDAC6 signaling pathway.