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Effect of prostaglandin analogs on matrix metalloproteinases and tissue inhibitor of metalloproteinases in eyelid muscle specimens

Authors Karli S, Ayala-Haedo JA, Feuer WJ, Fernandez M, Dubovy S, Wester ST

Received 24 June 2018

Accepted for publication 31 July 2018

Published 11 October 2018 Volume 2018:12 Pages 2039—2046

DOI https://doi.org/10.2147/OPTH.S178106

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Justinn Cochran

Peer reviewer comments 3

Editor who approved publication: Dr Scott Fraser


Sapir Karli, Juan Alfredo Ayala-Haedo, William J Feuer, Maria Fernandez, Sander Dubovy, Sara T Wester

Bascom Palmer Eye Institute, Miami, FL, USA

Purpose: To characterize the effect of prostaglandin analogs (PAs) on tissue specific expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) in levator aponeurosis resections (LAR) and conjunctiva-Muller muscle resections (CMMR).
Methods: Specimens from LAR and CMMR of PA users and non-users were analyzed for tissue specific expression of MMP-3, MMP-7, MMP-9 and TIMP-2 using immunohistochemistry. PA use, marginal reflex distances, levator function and palpebral fissure were documented through chart review. The associations between MMP expression, PA exposure time and ocular characteristics were evaluated with a two-factor analysis of variance and multiple correlation analysis.
Results: We observed a tissue specific pattern of expression of MMPs and TIMP-2 in relation to PA exposure between CMMR and LAR specimens. There was increased MMP-7 and TIMP-2 expression in muscle compared to collagen and adipose tissue (P≤0.005), as well as a statistically significant difference in the relationship of MMP-3, MMP-9 and TIMP-2 levels to PA exposure in the two types of muscles (all P≤0.011). Adipose tissue had a PA-dependent reduced expression of MMP-3 (P<0.022), which was seen in both LAR and CMMR. Decreased expression of MMP-3 in collagen correlated with increased dermatochalasis (P<0.045) and steatoblepharon (P<0.018).
Conclusion: PA exposure may affect MMP and TIMP expression in a tissue specific manner, and decreased expression of certain MMPs in collagen correlates to increased clinical measures of prostaglandin associated periorbitopathy (PAP). Further studies with larger samples are needed to ascertain if the changes associated with PAP are due to MMP/TIMP changes or to structural changes.

Keywords: MMP, matrix metalloproteinase, prostaglandin associated periorbitopathy, PAP, prostaglandin analog, periorbitopathy

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