Abstract
Purpose :
Keratoconus (KC) is a progressive corneal thinning disease that manifests in puberty and worsens during pregnancy. The onset and progression of KC is considered to be multifactorial and include: environmental, genetics, and hormonal imbalances; however, the pathobiology remains elusive. This study will reveal recent in vitro and in vivo findings related to sex hormones and their receptors in an attempt to establish a causal and contributory relationship to the KC disease process.
Methods :
In vitro: An established 3D in vitro self-assembled extracellular matrix (ECM) model was utilized in order to determine the interplay of major androgens/estrogens and the sex hormone receptors present in Healthy/KC corneal stromal cells via Western Blot analysis. In vivo: Ongoing clinical studies, focusing on sex hormones and KC, are discussed. Androgen/Estrogen ELISA expression was measured in a small cohort of KC patients before and after Collagen Cross Linking (CXL) treatment.
Results :
In vitro: Significant changes were observed between Healthy and KC corneas, as well as between males and females in the sex hormone receptors tested; androgen receptor (AR), progesterone receptor (PR), estrogen receptor alpha (ERα), and estrogen receptor beta (ERβ). For example, both estrone (E1) and estriol (E3) stimulation in Healthy-Females showed that AR, PR, and ERβ were significantly upregulated compared to Healthy-Males. In contrast, ERα and ERβ had significantly higher expression in HKC-Females, when compared to HKC-Males. In vivo: Using blood (plasma) levels, the levels of three essential sex hormones (DHEA-S, Estrone, and Estriol) were measured. After CXL, DHEA-S levels were lower but Estrone and Estriol levels were higher, suggesting that CXL not only affects the corneal tissue (i.e., locally), but also modulates hormonal levels in the bloodstream. Variability among patients, and changes due to medication/severity will also be discussed.
Conclusions :
Our data suggests that the human cornea is a sex-dependent and a hormone-responsive tissue. We posit that KC is a systemic disease, at least initially, and is heavily dependent on systemic and local hormone alterations.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.