Adipocytes influence choroidal neovascularization via PRDM16

Area of Science:

• Ophthalmology
• Metabolism
• Molecular Biology

Background:

• Neovascular age-related macular degeneration (nAMD) is a leading cause of vision loss in older adults, characterized by abnormal blood vessel growth (choroidal neovascularization - CNV).
• While genetics and age are risk factors, modifiable factors like body adiposity are increasingly implicated in AMD pathogenesis.
• The precise mechanisms linking adipose tissue to nAMD remain incompletely understood.

Purpose of the Study:

• To investigate the role of adipose tissue (AT), particularly adipocyte-specific pathways, in exacerbating CNV in a mouse model of nAMD.
• To identify specific molecular mediators within adipocytes that contribute to pathological angiogenesis in nAMD.

Main Methods:

• Laser-induced CNV model in mice to mimic nAMD.
• Analysis of gene expression changes in distal inguinal white AT (iWAT) following retinal injury.
• Selective deletion and reintroduction of the transcription factor Prdm16 in adipocytes.
• Ex vivo experimentation to assess theSecretory function of adipocytes.

Main Results:

• Laser-induced CNV upregulated browning and inflammatory genes in iWAT.
• Selective deletion of Prdm16 in adipocytes reduced AT browning and significantly inhibited CNV.
• Reintroducing Prdm16-expressing AT aggravated CNV in Prdm16-deficient mice.
• Prdm16-expressing adipocytes secreted angiogenic factors like IGFBP5, promoting pathological angiogenesis.

Conclusions:

• Prdm16-expressing adipocytes play a critical role in promoting CNV, a key feature of nAMD.
• This study highlights a novel communication pathway between distal adipose tissue and the retina in the pathogenesis of AMD.
• Targeting Prdm16 in adipocytes presents a potential therapeutic avenue for nAMD.