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

Abstract

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

Supplementary materials

Table S1 Type of surgery for PA treatment group and controls

Table S2 Demographics

Table S3 Time on PA

Table S4 Tissue specific differences in expression (SD)

Disclosure

The authors report no conflicts of interest in this work.