Elastin development-associated extracellular matrix constituents of subepithelial connective tissue in human pterygium

Invest Ophthalmol Vis Sci. 2014 Sep 2;55(10):6309-18. doi: 10.1167/iovs.14-14214.

Abstract

Purpose: We evaluated the expression of several extracellular matrix constituents implicated in the synthesis and reticulation of elastin in human pterygium, according to age and sex of the patients.

Methods: Pterygia and normal conjunctiva samples were divided into groups according to age (<50/≥50 years) and sex. Tissue was subjected to immunohistochemical staining with anti-lysyl oxidase (LOX), lyxyl oxidase-like 1 (LOXL-1), fibulin (FBLN)-5 and FBLN4, and fibrillin-1 (FBN1) antibodies. Specific primers for the same constituents were used in a quantitative real-time PCR (qRT-PCR) analysis to determine gene expression.

Results: The LOXL-1 (P = 0.0002), FBLN5 (P = 0.0035), and FBN1 (P < 0.0001) mRNAs were significantly higher in pterygium than conjunctiva. No differences were found for LOX and FBLN4 mRNA. The expression of LOXL-1 was not affected by age or sex; however, pterygium from men and patients over 50 years old exhibited significantly higher FBLN5/FBN1 expression than did controls. The LOX gene expression was higher in the pathologic samples from the over 50-year-olds compared to the conjunctiva (P = 0.0396) and in men's versus women's pterygium (P = 0.0173). In general, the levels of LOX, LOXL-1, and FBLN5 decreased with age in healthy samples, while the pathology seemed to have increased expression of the three proteins, and even more so in older patients. The FBLN4 and FBN1 immunostaining was slight in all samples, displaying no differences between groups.

Conclusions: Several extracellular matrix constituents, LOXs, FBN1, and FBLN5, implicated in the development of elastin, are overexpressed in the subepithelial connective tissue extracellular matrix of human pterygium, supporting our hypothesis that elastic synthesis and reticulation is dysregulated in this type of pathology.

Keywords: elastin; extracellular matrix; pterygium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Oxidoreductases / biosynthesis
  • Amino Acid Oxidoreductases / genetics
  • Conjunctiva / metabolism*
  • Conjunctiva / pathology
  • Connective Tissue / metabolism*
  • Connective Tissue / pathology
  • Elastin / biosynthesis
  • Elastin / genetics*
  • Extracellular Matrix / metabolism*
  • Extracellular Matrix / pathology
  • Extracellular Matrix Proteins / biosynthesis
  • Extracellular Matrix Proteins / genetics
  • Female
  • Gene Expression Regulation*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Pterygium / genetics*
  • Pterygium / metabolism
  • Pterygium / pathology
  • RNA, Messenger / genetics*
  • Real-Time Polymerase Chain Reaction

Substances

  • Extracellular Matrix Proteins
  • RNA, Messenger
  • Elastin
  • Amino Acid Oxidoreductases