title: Endocrine and Metabolic Pathways Linked to Keratoconus: Implications for the Role of Hormones in the Stromal Microenvironment.
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.
authors.affiliation: Department of Cell Biology/ University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: Tina B
authors.initials: TB
authors.lastname: McKay
authors.affiliation: Department of Ophthalmology, Aarhus University Hospital, Aarhus C DK-8000, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Hjortdal
authors.affiliation: Department of Ophthalmology, Aarhus University Hospital, Aarhus C DK-8000, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Sejersen
authors.affiliation: Division of Signal Transduction, Beth Israel Deaconess Medical and Department of Medicine, Harvard Medical School, Boston, MA USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Asara
authors.affiliation: Department of Ophthalmology/Dean McGee Eye Institute, Oklahoma City, OK 73104, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Cell Biology/ University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.|Department of Ophthalmology/Dean McGee Eye Institute, Oklahoma City, OK 73104, USA.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Karamichos
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D060833:Cellular Microenvironment; D002853:Chromatography, Liquid; D016207:Cytokines / Q000378:metabolism; D003710:Demography; D004703:Endocrine System / Q000378:metabolism*; D005260:Female; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D007640:Keratoconus / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D012463:Saliva / Q000378:metabolism; D012720:Severity of Illness Index; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D053719:Tandem Mass Spectrometry
chemical_list: D016207:Cytokines; D006728:Hormones; D018836:Inflammation Mediators