Abstract
Hormones play a critical role in regulating tissue function by promoting cell survival, proliferation, and differentiation. Our study explores the influence of endocrine function in regulating metabolism and inflammatory pathways in Keratoconus (KC), which is a corneal thinning disease associated with reduced stromal deposition. KC is known to be a multifactorial disease with an elusive pathogenesis. We utilized a cross-sectional study analyzing clinical features and saliva samples from sixty-four KC patients and fourteen healthy controls. In order to determine if endocrine function varied between healthy controls and KC, we measured hormone levels in saliva and found significantly increased dehydroepiandrosterone sulfate (DHEA-S) and reduced estrone levels in KC patients compared to healthy controls. We measured significant variations in metabolites associated with pro-inflammatory processes, including myoinositol and 1-methyl-histidine, by targeted mass spectrometry. We also measured significantly increased IL-16 and stem cell factor in KC saliva samples compared to healthy controls, with higher expression of these pro-inflammatory proteins correlating with increased KC clinical grade, corneal curvature, and stromal thinning. Our results identify a novel mechanism linking KC and pro-inflammatory markers and suggest that altered hormone levels modulate metabolism, cytokine, and growth factor expression leading to increased severity of the KC condition.
Highlights
Hormone production occurs in the major endocrine and exocrine organ systems in the human body, including the pituitary gland, thymus, pineal gland, thyroid, pancreas, ovaries, testes, adrenal glands, salivary glands, and sweat glands[1]
The purpose of our study was to elucidate the role of hormones and inflammation in the KC pathology by addressing the following questions: Is there a correlation between KC severity and hormone levels?, 2) Is systemic metabolism altered in KC that may drive a pro-inflammatory response?, and 3) Which cytokines or growth factors are elevated in KC leading to a more severe clinical presentation? In order to do so, we utilized a non-invasive method that has never been used before for the diagnosis or treatment of KC
Our results showed a significant reduction in estrone (1.3-fold, p = 0.0222) levels in KC saliva samples compared to healthy controls (Fig. 2A) with no significant differences in estriol or 17β -estradiol levels (Fig. 2B,C)
Summary
Hormone production occurs in the major endocrine and exocrine organ systems in the human body, including the pituitary gland, thymus, pineal gland, thyroid, pancreas, ovaries, testes, adrenal glands, salivary glands, and sweat glands[1]. Based on the early age of onset[29] and gender dominance[26,27,28] of KC, we hypothesized that altered hormone levels may play a role in KC development, with inflammatory factors contributing to a more severe disease phenotype.
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