Influence of the adipose tissue-retina axis on choroidal neovascularization

Abstract

Purpose : Obesity represents an important risk factor for neovascular age-related macular degeneration (nAMD). It is characterized by adipose tissue (AT) expansion via increased lipid storage in white adipocytes. Excessive weight gain is associated with inhibition of adipose tissue browning (i.e., conversion of white to beige adipocytes); a process implicated in thermogenesis, affecting systemic cytokine levels and glycemic control. However, whether AT browning can impact retinal homeostasis is unknown. We studied the influence of AT browning on the pathogenesis of nAMD.

Methods : Laser induced choroidal neovascularization (CNV) was induced by argon laser in male C57BL/6J, AQ:Prdm16^+/+ or AQ:Prdm16^-/- mice. AT browning and inflammation were assessed by qPCR and Western blots in white (WAT), beige (BgAT), and brown (BAT) adipose tissue during CNV. AT browning was inhibited by tamoxifen treatment of AQ:Prdm16^-/- mice. Impact of AT browning reintroduction on CNV was determined by adipose tissue transplant (ATT) of BgAT into browning deficient mice (AQ:Prdm16^-/- mice). CNV size was assessed in flatmounts of sclera-choroid-RPE.

Results : Three days after laser CNV, a significant induction of browning markers (UCP1 and PGC1α) was observed solely in BgAT. However, 14 days after CNV induction, UCP1 protein levels were significantly decreased in BgAT. qPCR analysis demonstrated a significant increase in pro-inflammatory markers in BgAT. Inhibition of AT browning in AQ:Prdm16^-/- mice significantly decreased CNV size, while reintroduction of BgAT via ATT significantly increased CNV size 14 days after CNV induction.

Conclusions : Our data demonstrates that laser CNV can trigger expression of browning markers and induce inflammation in AT. Inhibition of AT browning reduces CNV, whereas AT browning exacerbates CNV formation. These results suggest a potential role for deregulation of AT browning in nAMD.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.