Pseudoexfoliation syndrome: The critical role of the extracellular matrix in pathogenesis and treatment

Abstract

Pseudoexfoliation syndrome (PEXS) is an age-related condition manifesting mainly in ocular tissues. PEXS is manifested through excess aggregation of fibrillary extracellular material at the anterior part of the eye that consists of a plethora of biomolecules, such as different proteoglycans (PGs) and glycosaminoglycans. PEXS is often linked to increased intraocular pressure, and can also lead to pseudoexfoliation glaucoma with very poor prognosis. Various stimuli are known to affect PEXS, including oxidation stress (OS), UV radiation and osmotic pressure. OS, is prominently involved on the progression of the syndrome as it promotes fibrogenesis, possibly via the induction of transforming growth factor-β (TGF-β) and other biomolecular effectors. In addition, PEXS initiation is tightly connected with the dysregulation of extracellular matrix (ECM) homeostasis since aberrant expression of ECM molecules is linked to both the accumulation and low degradation of pseudoexfoliation material. This article aims at uncovering the crucial role of various ECM effectors such as lysyl oxidase-like proteins, matrix metalloproteinases, and TGF-β1, as well as the biochemical pathways involved in the development and the progression of the PEXS.

Analysis of genetically determined gene expression suggests role of inflammatory processes in exfoliation syndrome

“…Expression levels of ARID3B, CD276, INSYN1, LOXL1, NEO1, SCAMP2, STOML1 and UBL7 were measured in XFS (N = 12) and control (N = 19) eye tissues. We selected iris tissue because it is one of the tissues that are part of the anterior segment structures bathed by aqueous humor and upon which the flaky XFS materials are deposited [3][4][5]. Other affected structures include the trabecular meshwork, lens capsule, ciliary body, zonules and corneal endothelium [3][4][5].…”

“…We selected iris tissue because it is one of the tissues that are part of the anterior segment structures bathed by aqueous humor and upon which the flaky XFS materials are deposited [3][4][5]. Other affected structures include the trabecular meshwork, lens capsule, ciliary body, zonules and corneal endothelium [3][4][5]. All transcript levels were found to be decreased in iris tissues obtained from XFS patients compared to control samples, with significant differences for ARID3B, CD276, LOXL1, NEO1, SCAMP2 and UBL7 (p < 0.05) (Fig.…”

“…The exact pathophysiological processes that underline XFS is still unclear. However exfoliative material typically builds up at the anterior part of the eye, including in and around the trabecular meshwork slowing aqueous humor outflow and causing elevation in intraocular pressure [3][4][5]. It is the most common cause of secondary glaucoma, resulting in widespread global blindness [6].…”

Emerging roles of oxidative stress in the pathogenesis of pseudoexfoliation syndrome (Review)

“…Recently we have reviewed the critical role of ECM in pathogenesis and treatment and particularly the roles of ECM effectors and biochemical pathways involved in the development and the progression of the PEXS ( Fig. 1 ) ( 8 ). Here we further focused on the emerging roles of OS in PEXS.…”

“…As a result of the PEXM deposit on the lens capsule, a higher rate of open-angle glaucoma cataracts and resulting blindness was observed in most PEXS patients. In addition to the eye, deposits are also found around the blood vessels of the connective tissue and organs such as the lungs, heart, liver, kidneys, gallbladder, and meninges (8)(9)(10). Studies suggest that PEXM is associated with the development of systemic hypertension, myocardial infarction and cerebrovascular events.…”