let-7 Contributes to Diabetic Retinopathy but Represses Pathological Ocular Angiogenesis

Area of Science:

• Ophthalmology
• Molecular Biology
• Genetics

Background:

• The role of microRNAs (miRs) in diabetic retinopathy (DR) and age-related macular degeneration (AMD) is not fully understood.
• Let-7 family miRs are present in retinal and choroidal endothelial cells (ECs).

Purpose of the Study:

• To investigate the in vivo function of let-7 family miRs in the pathogenesis of DR and AMD.
• To elucidate the mechanisms by which let-7 affects endothelial cell function and pathological angiogenesis.

Main Methods:

• Overexpression and inhibition of let-7 in endothelial cells in vitro.
• Analysis of let-7 target gene HMGA2.
• Assessment of DR and choroidal neovascularization (CNV) phenotypes in let-7 transgenic mice and wild-type mice after laser injury.

Main Results:

• Let-7 overexpression repressed EC proliferation, migration, and networking in vitro.
• Silencing HMGA2 mimicked let-7 overexpression effects.
• Let-7 transgenic mice exhibited nonproliferative DR features but reduced CNV.
• Let-7 inhibition exacerbated laser-induced CNV.

Conclusions:

• Let-7 plays a causative role in nonproliferative diabetic retinopathy.
• Let-7 represses pathological angiogenesis, indicating distinct roles in DR and AMD pathogenesis.
• Let-7 represents a potential therapeutic target for retinal vascular diseases.