Lactylation-driven FTO targets CDK2 to aggravate microvascular anomalies in diabetic retinopathy

Abstract Diabetic retinopathy (DR) is a leading cause of irreversible vision loss in working-age populations. Fat mass and obesity-associated protein (FTO) is an N 6 -methyladenosine (m 6 A) demethylase that demethylates RNAs involved in energy homeostasis, though its influence on DR is not well studied. Herein, we detected elevated FTO expression in vitreous fibrovascular membranes of patients with proliferative DR. FTO promoted cell cycle progression and tip cell formation of endothelial cells (ECs) to facilitate angiogenesis in vitro, in mice, and in zebrafish. FTO also regulated EC-pericyte crosstalk to trigger diabetic microvascular leakage, and mediated EC–microglia interactions to induce retinal…

• NN
  National Natural Science Foundation of China

  Awards: 82070974, 82271100
• CA
  Chinese Academy of Sciences
• GO
  Government of Jiangsu Province
• NS
  Natural Science Foundation of Jiangsu Province

  Award: BK20231371
• NU
  Nantong University
• IO
  Institute of Biophysics, Chinese Academy of Sciences
• P3
  Project 333 of Jiangsu Province