Abstract
Glaucoma is a leading cause of blindness worldwide. Purpose of this study was to identify molecular markers that were significantly correlated with presence of glaucoma and outcome of glaucoma surgery. To accomplish this, we determined the profiles of pro-inflammatory cytokines in the aqueous humor of 101 glaucoma patients; 31 primary open angle glaucoma (POAG), 38 pseudoexfoliation glaucoma (PEG), and 32 neovascular glaucoma (NVG). We also studied 100 normal subjects as controls. In eyes with POAG or PEG, the level of interleukin (IL)-1α, IL-2, IL-4, IL-8, IL-23, and CCL2 were significantly elevated. In the NVG eyes, many inflammatory cytokines were also highly elevated. IL-8 had the highest odds ratio, and levels of IL-8 and CCL2 were significantly correlated with preoperative IOP or visual field defects in PEG eyes. Principal component analysis showed that IL-8 had the highest association to the IOP-cytokine component, and Cox proportional hazard model indicated that an elevation of IL-8 was a significant risk of filtering surgery failure. Together with modeling of their interactions and prognosis, IL-8 elevation is a significant risk factor both for detecting and managing glaucoma and may serve as a therapeutic target candidate to improve the prognosis of glaucoma surgery.
Highlights
Glaucoma is a leading cause of blindness worldwide
Our results showed that IL-5, IL-6, IL-8, IL-10, IL-15, IL-17, and CCL2 were significantly correlated with the intraocular pressure (IOP) levels in pseudoexfoliation glaucoma (PEG) eyes (Spearman correlation analysis, Fig. 3, IL-5 (ρ = 0.33, P = 0.0471), IL-6 (ρ = 0.47, P = 0.0036), IL-8 (ρ = 0.35, P = 0.0342), IL-10 (ρ = 0.39, P = 0.0202), IL-15 (ρ = 0.42, P = 0.0107), IL-17 (ρ = 0.40, P = 0.017), and CCL2 (ρ = 0.51, P = 0.0018))
When we assessed the association of the IOP with the cytokine levels, IL-8 and CCL2 had significant associations with the IOP elevation. Pathological changes, such as inflammation, ischemia, hypoxia, oxidative stress, endoplasmic reticulum (ER) stress, tissue remodeling, and fibrotic changes, in the trabecular outflow system have been reported to be associated with an elevation of the IOP
Summary
Glaucoma is a leading cause of blindness worldwide. Recent advances in diagnostic techniques have allowed clinicians to detect glaucoma effectively. Surgical interventions are required to reduce the elevated intraocular pressure (IOP) in eyes that are refractory to medications. An elevation of IOP can be caused by a decrease in the outflow of aqueous humor through the trabecular meshwork, Schlemm’s canal, and the collector channels. Fibrotic changes or deposits of extracellular matrix into the trabecular meshwork can slow or block the outflow which leads to an elevation of the IOP. Open angle glaucoma (OAG) often develops in eyes with the pseudoexfoliation syndrome which is associated with deposits of abnormal extracellular matrix in the meshwork tissue increasing the outflow resistance, and pseudoexfoliation glaucoma (PEG) often cause very high IOPs. Neovascular glaucoma (NVG) can cause very high IOPs, and the elevation is sustained. Neovascularization in the trabecular tissue and iris can cause severe inflammation which blocks aqueous outflow and an elevation of the IOP. No unified molecular signature or prognosis determinant has been determined for OAG and NVG, a determination of the molecular mechanisms of such markers should contribute to the development of new interventions or therapeutic strategies to manage such eyes
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