Lipocalin 2 is decreased in the serum of patients with Central Serous Chorioretinopathy: Towards a biomarker?

Abstract

Purpose : Two major forms of Central Serous chorioretinopathy (CSCR) are recognized depending on whether there is an associated clinically detectable epitheliopathy, that defines the chronicity. To date, no systemic biomarker of CSCR has been discovered.
Lipocalin 2 (Lcn2, Neutrophil gelatinase associated lipocalin, NGAL), binds retinoids and steroids and has multiple innate immune functions and also exist as a disulphide-linked heterodimer bound to MMP9. Lcn2, a biomarker of kidney diseases and heart failure is increased in AMD and retinitis pigmentosa patients. It was recently shown to protect human retinal pigment epithelial cells from oxidative stress-induced death.
Purpose : To measure the serum levels of Ngal and Ngal/MMP9 in CSCR patients (n=169) with (n=90) or without epitheliopathy (n=79) and in a cohort of 154 control patients.

Methods : Patients signed consent to give blood for research (CPP2016, 14390, DC-2016-2620).Control blood was obtained from French blood bank. Elisa Quantikine tests (R &D) were used to measure NGAL and NGAL/MMP9 complex. Patients with CRP>5mg/L, creatinine >100µmol/L, urea > 7.5 mmol/L were excluded. Levels were compared using non-parametric one way ANOVA test followed by a Kruskal-Wallis multiple comparison post-test.

Results : CSCR patients were 48.5 ± 11.8 years old with 84% of men. Control patients were 44 ±13 years old with 75% of men. The serum levels of lcn 2 (ng/ml ± SD) was 107±44 and the level of NGAL/MMP9 complex (ng/ml ± SD) was 76 ± 47 in the control group, and they were significantly lower in all CSCR patients (78 ± 35, p= 0.04 and 43.5± 37 p<0.0001 respectively). Lcn 2 was significantly lower both in the acute and in the chronic CSCR groups as compared to the control (p<0.001 and p=0.02). NGAL/MMP9 levels were significantly lower both in the acute CSCR and chronic CSCR groups versus control (p<0.0001 for both).

Conclusions : Serum levels of lcn2 are lower in patients with CSCR as compared to control, suggesting that systemic deregulation of the innate immune system and redox status may contribute to the disease. Serum lcn2 2 could serve to differentiate challenging CSCR cases from AMD. Further studies on larger cohorts are required to validate lcn2 as a CSCR biomarker.

This is a 2020 ARVO Annual Meeting abstract.