Proteomic Signature in Men with Central Serous Chorioretinopathy

To explore systemic contributors to central serous chorioretinopathy (CSCR) pathogenesis, we performed untargeted serum proteomics in 60 male CSCR patients (30 acute, 30 chronic) and 60 age-matched controls using label-free LC-MS/MS with stringent statistical pairing. Among 242 abundant proteins identified, 27 (11.5%) were significantly different in CSCR, converging on pathways of complement activation, coagulation, oxidative stress, immune regulation, and response to external stimuli. Complement cascade components (C1QA, C1S, C3, C4B, C8A/B/G, CFB) were upregulated, while the regulators CFHR1 and CFHR2 were decreased, contrary to age-related macular degeneration. Oxidative stress-related proteins (haptoglobin, hemoglobin subunits, peroxiredoxin-2) were elevated, consistent with prior evidence of systemic redox imbalance in CSCR. Tetranectin (CLEC3B) decreased and attractin (ATRN) increased in CSCR were validated by ELISA. Multiplex immunofluorescence on the human retina localized tetranectin to Müller cells, including the outer limiting membrane, and to the RPE and attractin to photoreceptor segments, retinal pigment epithelium, Bruch's membrane, and the choriocapillaris, supporting potential roles of both proteins at the retina-choroid interface. A distinct systemic proteomic signature in patients with CSCR highlights complement dysregulation, oxidative stress, and stress responses to external stimuli and identifies tetranectin and attractin as candidate biomarkers, which should further be validated in other cohorts.