Abstract
Purpose :
The pathomechanisms of chronic neurodegenerative glaucoma are complex and their interactions are still poorly understood. The main risk factor of elevated intraocular pressure may itself already be an epiphenomenon of other triggers, such as damaged trabecular meshwork cells that regulate aqueous humour (AqH) outflow. Altered expression of cytokines, including matrix metalloproteinases (MMP), are discussed in glaucoma. Extracellular matrix metalloproteinase inducer (EMMPRIN), an upstream inducer of several MMP, is suggested to be an important regulator of MMP production as shown in neurodegenerative disease such as Morbus Alzheimer or Multiple sclerosis. EMMPRIN and follistatin in the context of glaucoma are still totally understudied, but they probably participate in the regulation of extracellular matrix metabolism and may therefore be essential for regulation of the AqH outflow. The aim of the study is to determine whether cytokines in AqH of glaucoma patients show deviations in their abundance compared to healthy and, if so, to provide information about the mediators involved in the disease processes.
Methods :
The concentration of 34 proteins was determined by Luminex assay in AqH samples from patients with open angle glaucoma (n=87) and cataract patients as healthy control group (n=30).
Results :
The glaucoma group showed significantly higher levels of MMP-3, MMP-2, EMMPRIN, follistatin, LOX-1, endothelin-1, cortisol, and endostatin (p<0.05). In contrast, angiogenin was significantly less expressed in AqH of glaucoma patients (p<0.05). Elevated ocular EMMPRIN level correlated significantly positive with MMP-2 (r= 0.39, p=0.00018) and follistatin (r=0.27, p=0.01). Furthermore, AqH level of MMP-2 correlated significantly positive with the MMP-3 (r=0.34, p=0.001) and follistatin level (r= 0.39, p=0.0002).
Conclusions :
An alteration of the cytokine pattern in AqH of glaucoma patients could be shown. The positive correlation of EMMPRIN, MMP2 and follistatin points to their involvement in glaucoma pathology, most probably by regulating the extracellular matrix of trabekular mesh work and thereby the AqH outflow.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.