Conjunctival matrix metalloproteinases and their inhibitors in glaucoma patients

Abstract

ABSTRACT.Purpose: Chronic conjunctival inflammation, caused by various reasons, for example long-term use of topical drugs and/or their preservatives, affects the outcome of glaucoma surgery by interfering with wound healing. Matrix metalloproteinases (MMPs) remodel extracellular matrix (ECM) and are involved in the wound healing process. This study was designed to evaluate the conjunctival expression of MMPs and their tissue inhibitors (TIMPs) in the normal eye, primary open-angle glaucoma (POAG) and exfoliation glaucoma (ExG) and whether there is an association between staining intensities and deep sclerectomy outcome. Methods: Immunohistochemical procedures were performed on conjunctival samples which were obtained from POAG (n = 11) and ExG (n = 14) patients as well as normal (n = 7) subjects. Antibodies against MMPs (MMP-1, -2, -3 and -9) and TIMPs (TIMP-1, -2 and -3) were used. Results: In conjunctival stroma, expression levels of MMP-2 (p = 0.047), MMP-3 (p = 0.009), MMP-9 (p < 0.001), TIMP-1 (p = 0.003), TIMP-2 (p < 0.001) and TIMP-3 (p < 0.001) in ExG and MMP-9 (p = 0.008), TIMP-2 (p = 0.02) and TIMP-3 (p = 0.002) in POAG were significantly increased compared to control. We further found correlations between expression of MMP-1 and MMP-3 and the length of pilocarpine treatment. Conclusion: The expression of MMPs and TIMPs is increased in the conjunctiva of POAG and ExG patients having a long history of topical antiglaucoma drops. Antiglaucoma agents and/or their preservatives alter the remodelling balance of ECM in conjunctiva of POAG and ExG eyes. The balance between MMPs and TIMPs may play a crucial role in the conjunctival wound healing process and the outcome of glaucoma surgery.

Oxidized low‐density lipoprotein, lipid and calcium aggregates reveal oxidative stress and inflammation in the conjunctiva of glaucoma patients

“…In our recently published study, we also found increased expressions of certain MMPs and tissue inhibitors of metalloproteinases (TIMPs) in the conjunctival tissue of glaucoma patients (Helin‐Toiviainen et al. ) which may be an indicator of altered tissue ECM remodelling in patient samples and it may further have an influence in the normal wound healing process. Thus, it is possible that there is a connection between chronic inflammation, alterations in tissue remodelling (Helin‐Toiviainen et al.…”

“…Thus, it is possible that there is a connection between chronic inflammation, alterations in tissue remodelling (Helin‐Toiviainen et al. ; Välimäki & Uusitalo ) expression of extracellular matrix proteins (Välimäki & Uusitalo ) and lipid accumulation resembling a wound healing cascade similar to atherosclerotic plaque formation. These alterations may interfere with the normal wound healing process eventually influencing surgical outcome.…”

Effects of sustained daily latanoprost application on anterior chamber anatomy and physiology in mice

“…Several studies have assessed changes in gene transcription following latanoprost treatment 22 , 50 – 53 . Thus, at the conclusion of our study, we collected tissues for the analysis of candidate genes in the cornea and iris.…”

Interaction Between Pilocarpine and Ripasudil on Intraocular Pressure, Pupil Diameter, and the Aqueous-Outflow Pathway

“…First, we studied only short-term responses to the drugs. Both pilocarpine and ROCK inhibitors can affect the extracellular matrix, 18,36,42,48 so a longer period of evaluation after dosing is required. Second, the doses we used in vitro may differ from those in the eye.…”