Corneal Expression of SLURP-1 by Age, Sex, Genetic Strain, and Ocular Surface Health

Invest Ophthalmol Vis Sci. 2015 Dec;56(13):7888-96. doi: 10.1167/iovs.15-18206.

Abstract

Purpose: Although secreted Ly6/urokinase-type plasminogen activator receptor-related protein-1 (Slurp1) transcript is highly abundant in the mouse cornea, corresponding protein expression remains uncharacterized. Also, SLURP1 was undetected in previous tear proteomics studies, resulting in ambiguity about its baseline levels. Here, we examine mouse corneal Slurp1 expression in different sexes, age groups, strains, and health conditions, and quantify SLURP1 in human tears from healthy or inflamed ocular surfaces.

Methods: Expression of Slurp1 in embryonic day-13 (E13), E16, postnatal day-1 (PN1), PN10, PN20, and PN70 Balb/C, FVBN, C57Bl/6, and DBA/2J mouse corneas, Klf4Δ/ΔCE corneas with corneal epithelial-specific ablation of Klf4, migrating cells in wild-type corneal epithelial wound edge, and in corneas exposed to pathogen-associated molecular patterns (PAMPs) poly(I:C), zymosan-A, or Pam3Csk4 was examined by QPCR, immunoblots, and immunofluorescent staining. Human SLURP1 levels were quantified by ELISA in tears from 34 men and women aged 18 to 80 years.

Results: Expression of Slurp1, comparable in different strains and sexes, was low in E13, E16, PN1, and PN10 mouse corneas, and increased rapidly after eyelid opening in a Klf4-dependent manner. We found Slurp1 was downregulated in corneas exposed to PAMPs, and in migrating cells at the wound edge. Human SLURP1 expression, comparable in different sexes and age groups, was significantly decreased in tears from inflamed ocular surfaces (0.34%) than those from healthy individuals (0.77%).

Conclusions: These data describe the influence of age, sex, genetic background, and ocular surface health on mouse corneal expression of Slurp1, establish the baseline for human tear SLURP1 expression, and identify SLURP1 as a useful diagnostic and/or therapeutic target for inflammatory ocular surface disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Animals
  • Antigens, Ly / biosynthesis
  • Antigens, Ly / genetics*
  • Cell Movement
  • Cornea / metabolism*
  • Cornea / pathology
  • Corneal Diseases / genetics*
  • Corneal Diseases / metabolism
  • Corneal Diseases / pathology
  • DNA / genetics*
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Expression Regulation*
  • Humans
  • Immunoblotting
  • Kruppel-Like Factor 4
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Middle Aged
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sex Factors
  • Tears / metabolism
  • Urokinase-Type Plasminogen Activator / biosynthesis
  • Urokinase-Type Plasminogen Activator / genetics*
  • Young Adult

Substances

  • Antigens, Ly
  • KLF4 protein, human
  • Klf4 protein, mouse
  • Kruppel-Like Factor 4
  • SLURP-1 protein, mouse
  • DNA
  • Urokinase-Type Plasminogen Activator