# ET-1, MMPs, ZAG, and APN Link Reduced Ocular Perfusion to Glaucoma

## TL;DR

This study links specific proteins and peptides to reduced blood flow in the eye, which is associated with glaucoma.

## Contribution

The study identifies ET-1, APN, MMP-3, ZAG, and other proteins as potential biomarkers for impaired ocular perfusion in glaucoma.

## Key findings

- Glaucomatous eyes show reduced retinal nerve fiber layer thickness and vessel density.
- Elevated levels of ET-1, MMP-3, ZAG, and APN in aqueous humor correlate with impaired ocular perfusion.
- Multivariable analysis confirms a link between APN levels and reduced vessel density in glaucoma.

## Abstract

Purpose: This study sets out to analyze the correlation of ET-1, a vasoactive peptide, along with various cytokines and vascular factors, with clinical parameters and OCT/OCT-A measurements in glaucoma participants. Methods: Eyes of participants with cataract (n = 30) or glaucoma (n = 87) were examined with optical coherence tomography (OCT) and OCT angiography (OCT-A). Aqueous humor (AqH) from the examined eye and plasma were sampled during cataract or glaucoma surgery and analyzed by means of ELISA and Luminex assay to determine their levels of ET-1 and 35 proteins deemed relevant for regulation of the AqH outflow pathway, ocular perfusion (OP), and glucose metabolism. Results: Glaucomatous eyes are characterized by reductions in RNFL thickness and OP, reflected by reduced vessel density. Furthermore, significantly elevated peripheral ET-1 levels were detected in participants with glaucoma. In addition, significantly elevated AqH levels of MMP-2, MMP-3, ET-1, sEMMPRIN, ZAG, sLOX-1, follistatin, cortisol, endostatin, sTIE-2, and PDGF-BB were detected in the glaucomatous eyes, with correlation to reduced VD for APN, C3a, MMP-3, resistin, sTIE-2, and ZAG. Multivariable analysis showed a correlation of AqH APN levels with the reduced VD in glaucomatous eyes. Conclusions: The peripheral ET-1 level and the intraocular levels of APN, C3a, MMP-3, resistin, sTIE-2, and ZAG are associated with impaired OP in glaucoma. Furthermore, elevated intraocular levels of MMP-3, ZAG, and APN were identified as biomarkers for impaired perfusion in glaucoma.