Abstract

No systemic biomarker of Central Serous Chorioretinopathy (CSCR) has been identified. Lipocalin 2 (LCN2 or NGAL), alone or complexed with MMP-9 (NGAL/MMP-9), is increased in several retinal disorders. Serum levels of LCN2 and NGAL/MMP-9 were measured in CSCR patients (n = 147) with chronic (n = 76) or acute/recurrent disease (n = 71) and in age- and sex-matched healthy controls (n = 130). Samples with CRP > 5 mg/L, creatinine > 100 ”mol/L, and/or urea > 7.5 mmol/L were excluded. Serum LCN2 was lower in CSCR patients than controls (81.4 ± 48.7 vs 107.3 ± 44.5 ng/ml, p < 0.0001), and lower in acute/recurrent CSCR than controls (p < 0.001) and chronic CSCR (p = 0.006). Serum NGAL/MMP-9 was lower in CSCR patients than controls (47.2 ± 40.7 vs 74.1 ± 42.6, p < 0.0001), and lower in acute/recurrent CSCR than controls (p < 0.001) and chronic CSCR (p = 0.002). A ROC curve showed that for LCN2 serum levels, the 80-ng/ml cutoff value allows to discriminate acute/recurrent CSCR from controls with 80.3% sensitivity and 75.8% specificity, and for NGAL/MMP-9 serum levels, a 38-ng/ml cutoff value allows to discriminate acute/recurrent CSCR from controls with 69.6% sensitivity and 80.3% specificity. In both acute and chronic CSCR, low serum LCN2 and NGAL/MMP-9, provide a biological link between the two CSCR forms, and potential susceptibility to oxidative stress and innate immune dysregulation in CSCR.

Highlights

  • No systemic biomarker of Central Serous Chorioretinopathy (CSCR) has been identified

  • Since OCT-A was not available in all clinics at the time of cohorts constitution, choroidal neovascularization (CNV) secondary to CSCR could not be excluded with certainty, patients suspected of CNV on spectral domain optical coherence tomography (SD-OCT) were excluded if CNV was confirmed on indocyanine green (ICG)

  • Serum levels of LCN2 (NGAL) and Neutrophil Gelatinase-Associated Lipocalin (NGAL)/MMP‐9 are lower in CSCR than in control sub‐ jects

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Summary

Introduction

No systemic biomarker of Central Serous Chorioretinopathy (CSCR) has been identified. Serum levels of LCN2 and NGAL/MMP-9 were measured in CSCR patients (n = 147) with chronic (n = 76) or acute/recurrent disease (n = 71) and in age- and sex-matched healthy controls (n = 130). Lipocalin-2 (LCN2), whose human ortholog is Neutrophil Gelatinase-Associated Lipocalin (NGAL), is a 25-kD secreted protein, expressed in numerous cell types and organ systems, such as innate immune cells, epithelial cells, and brain astrocytes. In the eye, it is expressed in retinal pigment epithelial c­ ells[8] and in retinal glial MĂŒller cells 9. LCN2 protected human RPE cells derived from induced pluripotent stem cells (iPS-RPE cells) against oxidative stress by increasing the expression of the antioxidant enzymes HMOX1 (Heme oxygenase 1) and SOD2 (superoxide dismutase 2)[15], suggesting that LCN2 exerts important neuroprotective effects in the outer retina

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