Intravitreal Metformin Protects Against Choroidal Neovascularization and Light-Induced Retinal Degeneration

Area of Science:

• Ophthalmology
• Pharmacology
• Cell Biology

Background:

• Neovascular age-related macular degeneration (nAMD) is a leading cause of vision loss in older adults.
• Current treatments for nAMD, primarily intravitreal anti-angiogenic agents, are expensive and moderately effective.
• Metformin, a common anti-diabetic medication, has demonstrated potential in mitigating aging, angiogenesis, and inflammation.

Purpose of the Study:

• To investigate the anti-angiogenic and neuroprotective effects of intravitreal metformin in preclinical models of nAMD.
• To assess metformin's impact on choroidal neovascularization (CNV) and light-induced retinal degeneration.

Main Methods:

• Preclinical assessment of metformin's effect on vessel growth using choroidal explants.
• Intravitreal administration of metformin in laser-induced CNV and light-induced retinal degeneration mouse models (C57BL/6J and BALB/cJ).
• Analysis of gene expression related to angiogenesis and inflammation in the choroid and retinal pigment epithelium.

Main Results:

• Metformin demonstrated a dose-dependent reduction in new vessel growth in choroidal explants.
• Intravitreal metformin suppressed CNV formation and reduced macrophage/microglia infiltration in laser-induced models.
• Metformin provided protection against retinal thinning in light-induced degeneration models and downregulated pro-angiogenic and pro-inflammatory genes.

Conclusions:

• Metformin exhibits significant anti-angiogenic and neuroprotective properties relevant to nAMD.
• Intravitreal metformin presents a potential accessible therapeutic option for managing nAMD.
• Further research into metformin as an nAMD treatment is warranted based on these preclinical findings.