Transthyretin-Regulated Diabetic Retinopathy Through the VEGFA/PI3K/AKT Pathway

Area of Science:

• Ophthalmology
• Endocrinology
• Molecular Biology

Background:

• Transthyretin (TTR) is implicated in various diabetes-related conditions.
• Diabetic retinopathy (DR) is a significant microvascular complication of diabetes.
• The molecular mechanisms underlying DR, particularly involving TTR, require further elucidation.

Purpose of the Study:

• To investigate the role of Transthyretin (TTR) in the pathogenesis of diabetic retinopathy (DR).
• To determine if TTR influences DR progression via the Vascular Endothelial Growth Factor A (VEGFA)/Phosphatidylinositol 3-kinase (PI3K)/Protein Kinase B (AKT) signaling pathway.

Main Methods:

• Established in vitro models using human retinal microvascular endothelial cells (hRMECs) exposed to high glucose (HG).
• Developed an in vivo diabetic retinopathy (DR) model in C57BL/6J mice using streptozotocin (STZ) injection.
• Assessed cell proliferation, migration, and angiogenesis; analyzed retinal tissue morphology; quantified protein levels (VEGFA, CD31, PI3K, AKT) via ELISA, immunohistochemistry, immunofluorescence, and Western blot.

Main Results:

• TTR treatment reversed high glucose-induced increases in hRMEC proliferation, migration, and angiogenesis, while decreasing apoptosis.
• TTR inhibited high glucose-induced upregulation of VEGFA, PI3K p-p85, and p-AKT in hRMECs.
• In vivo studies confirmed that TTR alleviates DR progression in a mouse model, demonstrating its protective effect on retinal tissues.

Conclusions:

• Transthyretin (TTR) significantly mitigates the progression of diabetic retinopathy (DR).
• TTR exerts its protective effects by molecularly modulating the VEGFA/PI3K/AKT signaling axis.
• These findings highlight TTR as a potential therapeutic target for managing diabetic retinopathy.