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Published on: September 23, 2022
Expression of MMPs and TIMPs in human pterygia and cultured pterygium epithelial cells
N Di Girolamo1, P McCluskey, A Lloyd
1Inflammation Research Unit, School of Pathology, The University of New South Wales, Sydney, Australia. n.digirolamo@unsw.edu.au
Purpose:
Pterygia are a common, benign, fibrovascular, and infiltrative process of the corneal-conjunctival junction of unknown pathogenesis. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes active against all components of the extracellular matrix, whose activity is specifically neutralized by tissue inhibitors of MMPs (TIMPs). In the current study the hypothesis was that MMPs and TIMPs may actively participate in the formation and progression of pterygia.
Methods:
In this study, 25 pterygium specimens and 15 normal conjunctival biopsies obtained from subjects undergoing surgery for glaucoma and cataract, were processed for immunohistochemistry or in situ hybridization. Pterygium epithelial cells (PECs) were cultured under serum-free conditions and exposed to proinflammatory cytokines to determine both the mRNA and protein expression profiles of MMPs and TIMPs.
Results:
Collagenase-1 and gelatinase A were expressed in all pterygia examined, specifically localized to the epithelium (directly adjacent to collagen type III), with gelatinase B expression exclusively associated with neutrophils. No collagenase-1 or gelatinase A was detected in normal conjunctiva. TIMP-1 and -3 were localized to epithelial cells with additional TIMP-3 immunoreactivity detected in the extracellular matrix, endothelial cells and leukocytes of all diseased tissue. TIMP-3 protein was evident in 4 of 15 normal conjunctiva. Induction of collagenase-1, gelatinase A, and TIMP-1 mRNA and protein was demonstrated in epithelial cells treated with tumor necrosis factor-alpha and interleukin-1alpha, whereas TIMP-3 expression was unaltered.
Conclusions:
This is the first study to document the cellular expression of MMPs and TIMPs in pterygia and cultured human PECs. MMPs and TIMPs may contribute to the inflammation, tissue remodeling, and angiogenesis that characterize pterygia. Understanding the role these proteins play may lead to novel therapies intended to reduce the progressive nature of pterygia.
Insights
Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) are present in pterygia. These proteins may play a role in pterygium formation and progression, suggesting potential therapeutic targets.
Area of Science:
- Ophthalmology
- Molecular Biology
- Cell Biology
Background:
- Pterygia are common, benign growths on the corneal-conjunctival junction with unknown causes.
- Matrix metalloproteinases (MMPs) degrade extracellular matrix, while tissue inhibitors of MMPs (TIMPs) neutralize them.
- The role of MMPs and TIMPs in pterygium pathogenesis is not well understood.
Purpose of the Study:
- To investigate the expression and potential role of MMPs and TIMPs in pterygium tissue and cultured pterygium epithelial cells (PECs).
- To test the hypothesis that MMPs and TIMPs actively participate in pterygium formation and progression.
Main Methods:
- Immunohistochemistry and in situ hybridization were used on 25 pterygium specimens and 15 normal conjunctival biopsies.
- Pterygium epithelial cells (PECs) were cultured and treated with proinflammatory cytokines (TNF-α, IL-1α) to assess MMP and TIMP expression.
Main Results:
- Collagenase-1 and gelatinase A were found in all pterygia but not in normal conjunctiva.
- Gelatinase B was associated with neutrophils in pterygia.
- TIMP-1 and TIMP-3 were localized to epithelial cells and other cells in pterygia; TIMP-3 was also found in some normal conjunctiva.
- Proinflammatory cytokines induced MMPs and TIMP-1 but not TIMP-3 in cultured PECs.
Conclusions:
- This study is the first to show cellular expression of MMPs and TIMPs in pterygia and cultured PECs.
- MMPs and TIMPs likely contribute to pterygium inflammation, tissue remodeling, and angiogenesis.
- Further understanding of MMP and TIMP roles may lead to new therapies for pterygia.
