Proinflammatory Cytokines Are Involved in the Initiation of the Abnormal Matrix Process in Pseudoexfoliation Syndrome/Glaucoma

Abstract

Pseudoexfoliation (PEX) syndrome, which is an age-related, generalized elastotic matrix process, currently represents the most common identifiable risk factor for open-angle glaucoma. Dysregulated expression of proinflammatory cytokines has been implicated in the initiation of various fibrotic disorders and in the pathophysiology of glaucoma. Here we investigated the presence, expression, regulation, and functional significance of proinflammatory cytokines in eyes with early and late stages of PEX syndrome/glaucoma in comparison with normal and glaucomatous control eyes using multiplex bead analysis, immunoassays, real-time PCR, Western blotting, immunohistochemistry, and cell culture models. Early stages of PEX syndrome were characterized by approximately threefold (P < 0.005) elevated interleukin (IL)-6 and IL-8 levels in the aqueous humor and a concomitant approximately twofold (P < 0.001) increase in mRNA expression levels in anterior segment tissues as compared with controls. In contrast, late stages of PEX syndrome/glaucoma did not differ significantly from controls. IL-6, IL-6 receptor, and phospho-signal transducer and activator of transcription 3 could be mainly localized to walls of iris vessels and to the nonpigmented epithelium of ciliary processes. IL-6 and IL-8 were significantly up-regulated by ciliary epithelial cells in response to hypoxia or oxidative stress in vitro, whereas IL-6, but not IL-8, induced the expression of transforming growth factor-beta1 and elastic fiber proteins. These findings support a role for a stress-induced, spatially, and temporally restricted subclinical inflammation in the onset of the fibrotic matrix process characteristic of PEX syndrome/glaucoma.

Elevated neutrophil-to-lymphocyte ratio in pseudoexfoliation syndrome

“…11 Proinflammatory cytokines in eyes with early and late stages of PEX syndrome/glaucoma were studied. 12 The authors support a role for a stressinduced, spatially, and temporally restricted subclinical inflammation in the onset of the fibrotic matrix process characteristic of PEXS/PEXG. 12 Sorkhabi et al studied high-sensitivity C-reactive protein and tumor necrosis factor alpha in PEXS and mentioned that increased levels of these markers, as signs of inflammation and peripheral endothelial dysfunction, may be risk factors for systemic and ocular manifestations of PEXS.…”

“…12 The authors support a role for a stressinduced, spatially, and temporally restricted subclinical inflammation in the onset of the fibrotic matrix process characteristic of PEXS/PEXG. 12 Sorkhabi et al studied high-sensitivity C-reactive protein and tumor necrosis factor alpha in PEXS and mentioned that increased levels of these markers, as signs of inflammation and peripheral endothelial dysfunction, may be risk factors for systemic and ocular manifestations of PEXS. 13 In contrast, high-sensitivity C-reactive protein had not been found as a predictive marker of inflammation and peripheral endothelial dysfunction in PEXS and PEXG.…”

Pseudoexfoliation syndrome in chronic kidney disease patients

“…The findings suggested that an increased expression of IL-6 and IL-8, which may be induced by chronic stress conditions, such as oxidative stress and hypoxia, may act as a triggering factor for the abnormal PEX material production in the early stages. 14 It is accepted that oxidative stress contributes to atherosclerosis and also to kidney injury. Antioxidant mechanisms are inefficient in chronically hemodialyzed patients, which result in increased formation of reactive oxygen species and other free radicals and consequently in oxidative stress.…”

Pseudoexfoliation glaucoma: Always actual problem in ophthalmology

“…Pseudoeksfolijacije su sistemski metabolički poremećaj vezivnog tkiva, verovatno nastao kao rezultat poremećaja sinteze i rasporeda mikrofibrila (23). Dugo se smatralo da je u pitanju poremećaj metabolizma bazalne membrane.…”