Abstract

Diabetic retinopathy (DR) is a leading cause of vision impairment, yet the role of chemerin receptor 23 (ChemR23) in its progression remains unclear. This study aimed to explore the function of ChemR23 in modulating Müller cells' activation and injury to retinal ganglion cells (RGCs) in DR. Using 75 db/db and 16 wild-type mice divided into eight groups, we assessed ChemR23 expression and its interaction with phosphatase and tensin homolog (PTEN) through molecular docking and surface plasmon resonance. Immunofluorescence confirmed the co-localization of ChemR23 with glutamine synthetase (GS) and PTEN in Müller cells. Histological evaluation revealed retinal thinning and RGCs in 18-week db/db mice, accompanied by reduced synaptic markers (SYN, PSD95) and PTEN, alongside elevated glial fibrillary acidic protein, inflammatory cytokines, and phosphorylated protein kinase B (AKT). Activation of ChemR23 with Resolvin E1 (RvE1) or Chemerin 9 (C9) ameliorated these pathological changes. However, the protective effects were abolished by the PTEN inhibitor SF1670. These findings demonstrate that ChemR23 may regulate AKT phosphorylation through its interaction with PTEN, thereby protecting the retinal neurons and suppressing inflammatory responses and Müller cell activation in DR.