Abstract
Purpose :
The transforming growth factor-beta (TGF-β) superfamily are essential regulators of corneal wound healing cascades. Specifically, TGF-β1 (T1) is known to induce corneal fibrosis, while TGF-β3 (T3) prevents fibrosis. Currently, the effects of sex as a variable in corneal wound healing is largely unknown. The aim of this study was to investigate the interplay between TGF-β1/β3 and sex hormone receptors in the corneal stroma, and highlight the differences between sexes.
Methods :
Primary human corneal fibroblasts (HCFs) from healthy, age-matched, donors were isolated and plated on 6-well transwell plates (3D constructs) at a density of 1 x 106/well for 4 weeks. HCFs were supplemented with stable 0.5mM Vitamin C (Controls) and stimulated with T1 (0.1 ng/mL) or T3 (0.1 ng/mL). Protein expressions of Androgen Receptor (AR), Progesterone Receptor (PR), Estrogen Receptor Alpha (ERα), Estrogen Receptor Beta (ERβ), Luteinizing Hormone Receptor (LHR), Follicle-Stimulating Receptor (FSHR), Gonadotropin Releasing Hormone Receptor (GNRHR) were analyzed using Western Blot analysis.
Results :
Our data revealed that T1 treatment, in females, caused significant upregulation in the expression of AR, PR, ERα, FSHR, and GnRHR when compared to controls. In males, T1 led to significant downregulation of FSHR but caused significant upregulation in the expressions ERα, ERβ, and GnRHR. T3 treatment in females, caused significant upregulation in the expression of PR, ERα, ERβ, LHR, FSHR, and GNRHR. Interestingly, T3 treatments in males, led to significant downregulation in the expressions AR, ERα, and FSHR.
Conclusions :
Our data suggests significant modulation of sex hormone receptors by both TGF-β isoforms. We observed that sex hormone receptors were more widely expressed in females compared to males, following T1/T3 treatments. Interestingly, T1 and T3 treatments both caused sex-specific modulation of FSHR, while T3 only led to opposite effects in ERα between sexes. Further studies are warranted in order to fully delineate the role of sex hormones receptors in corneal fibrosis.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.