Abstract
Purpose :
Nonarteritic anterior ischemic optic neuropathy (NAION) is a leading cause of irreversible vision loss in those older than 50. We investigated the plasma proteome of patients with NAION and its biological activity on the retina and optic nerve.
Methods :
We obtained plasma from 38 subjects (10 controls, 9 acute, 8 chronic unilateral and 11 chronic bilateral NAION patients) and performed proteomic analysis using mass spectrometry. Data was analyzed using logistic regression, dimensionality reduction and pathway analysis to identify NAION biomarker candidates. We next investigated the effect of NAION plasma on primary human retinal astrocytes in vitro and in a rodent NAION model of photochemical thrombosis. Analysis of retina edema, gliosis and neuronal survival was performed using optical coherence tomography in vivo imaging and histology of the retina and optic nerve.
Results :
We identified 38 blood biomarker candidates for NAION, which were mostly associated to complement system and fibrinolysis pathways. Plasma from chronic bilateral NAION patients increased mRNA levels of Gfap and complement protein C3 in human retinal astrocytes. Intraocular injection of NAION plasma after photochemical thrombosis exacerbated retinal edema, led to dysfunctional Kir4.1 expression in astrocytes, and decreased neuronal survival at week 3 post-NAION.
Conclusions :
Plasma from NAION patients have distinguishable levels of proteins associated with complement pathways and fibrinolysis and have detrimental biological activity on the retinal glia and neurons. Our findings highlight potential molecular targets for NAION biomarker development and treatment.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.