Correlational Analysis of Qiming Granule with the CMKLR1-Centered Network and Systemic Inflammation via the Gut–Retina Axis in Diabetic Retinopathy

Diabetic retinopathy (DR) is a neurovascular complication driven by chronic hyperglycemia and systemic inflammation, with emerging evidence highlighting the gut-retina axis as a critical but underexploited therapeutic target. This study investigates whether Qiming Granule (QMG) exerts its protective efficacy against DR by modulating the gut-retina axis. C57BL/6 mice were randomized into experimental groups and subjected to distinct interventions. Retinal histopathological changes were assessed by Hematoxylin-Eosin (HE) staining. Serum levels of inflammatory cytokines (IL-1β, IL-6, TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA). The expression of key regulatory proteins (CMKLR1, Wnt5a, PPAR-γ, AP-1, TP53) in both retinal and colonic tissues was detected by Western blot (WB). Gut microbiota composition and diversity were characterized by full-length 16S rDNA sequencing. Correlational analyses were performed to assess relationships between gut microbiota and inflammatory factors or key proteins. QMG treatment improved retinal histopathological abnormalities, as evidenced by restoration of retinal laminar architecture, partial recovery of retinal ganglion cell numbers (P < 0.001), and reversal of retinal thinning (P < 0.01). It also markedly downregulated serum IL-1β, IL-6, and TNF-α levels (P < 0.0001). Along the gut‑retina axis, QMG reversed the abnormal expression of key regulatory proteins, notably the CMKLR1‑centered network (Wnt5a, PPAR-γ, AP-1, TP53). Furthermore, QMG restored gut microbiota composition, diversity, and function, and correlation analyses revealed that QMG couples systemic inflammation with these regulatory proteins to modulate the gut‑retina axis. This study provides preliminary pharmacological evidence that QMG ameliorates DR by coupling the CMKLR1-centered regulatory network (including Wnt5a, PPAR-γ, AP-1, and TP53) and systemic inflammation via the gut-retina axis, positioning QMG as a promising gut-retina therapeutic strategy for DR.