Insulin-like factor 3 promotes wound healing at the ocular surface

Area of Science:

• Ophthalmology
• Endocrinology
• Cell Biology

Background:

• Tear fluid contains hormones crucial for ocular surface homeostasis.
• Insulin-like factor 3 (INSL3) and its receptor RXFP2 (relaxin/insulin-like family peptide receptor 2) roles at the ocular surface are unknown.

Purpose of the Study:

• To investigate the presence and function of INSL3 and RXFP2 at the ocular surface and in tears.
• To determine the role of INSL3 in ocular surface homeostasis and corneal wound healing.

Main Methods:

• RT-PCR and ELISA were used to detect INSL3 and RXFP2 expression in ocular tissues, cell lines, and tears.
• Cell proliferation, migration, and gene expression (MMP2, MMP9, MMP13, TIMP1, TIMP2) were analyzed after stimulation with recombinant human INSL3 (hrINSL3).
• A mouse corneal defect model was used to assess the effect of topical hrINSL3 on wound healing.

Main Results:

• INSL3 and RXFP2 transcripts and INSL3 protein were detected in ocular tissues, cell lines, and tears.
• Higher INSL3 concentrations were found in male tears compared to female tears.
• hrINSL3 stimulation increased proliferation in conjunctival and sebaceous cells and migration in conjunctival cells.
• hrINSL3 regulated MMP2, TIMP1, and TIMP2 expression.
• Topical hrINSL3 accelerated corneal wound healing in mice.

Conclusions:

• INSL3 and RXFP2 play a novel, gender-specific role in ocular surface homeostasis.
• INSL3 promotes corneal wound healing, suggesting a potential therapeutic application.