SEARCHOTHERophthalmology, cornea

other·ophthalmology, cornea, preclinical research, biomedical research, endocrinology·PMC10726429

Selective Modulation of the Keratoconic Stromal Microenvironment by FSH and LH

The American Journal of Pathology · 7 authors, 4 centres

AI SUMMARY

FIDELITY 100%

POPULATIONPrimary human corneal fibroblasts (HCF) and human keratoconus (HKC) cells

INTERVENTIONStimulation with 2.5 or 10 mIU/mL FSH and 5 or 35 mIU/mL LH in a 3D self-assembled matrix

COMPARISONHealthy corneal fibroblasts vs. human keratoconus cells; with and without FSH/LH stimulation

This summary was generated by AI from a single paper. It has not been reviewed by a clinician and is not clinical advice. Verify against the source before acting on it.

AGENT 01 · STRUCTURED SUMMARY

TRACE TO SOURCE

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TL;DR

This preclinical study used a 3D in vitro model of human corneal cells to investigate the effects of the gonadotropins FSH and LH. It found that LH, but not FSH, selectively increased proliferation and decreased fibrosis markers in keratoconic cells compared to healthy cells.

Full summary

1,073 CHARS

This study utilized a three-dimensional, self-assembled matrix in vitro model to investigate the role of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in the keratoconus (KC) stromal microenvironment. Healthy corneal fibroblasts and human KC cells were cultured and stimulated with stable vitamin C, then treated with FSH or LH. The central result was that LH stimulation led to significantly greater proliferation in human KC cells compared to healthy cells, and it significantly altered the expression of sex hormone receptors, fibrotic markers, proteoglycans, and signaling pathway members. In contrast, FSH stimulation produced no significant changes in proliferation. The findings suggest that exogenous LH has a selective impact on the KC microenvironment, potentially influencing fibrosis and extracellular matrix remodeling. Limitations include the in vitro nature of the model, which does not capture the full complexity of in vivo KC pathogenesis, and the inability to definitively determine the role of hormone receptors in disease progression.

PICO

PPOPULATION

Primary human corneal fibroblasts (HCF) and human keratoconus (HKC) cells

IINTERVENTION

Stimulation with 2.5 or 10 mIU/mL FSH and 5 or 35 mIU/mL LH in a 3D self-assembled matrix

OOUTCOME

Cell proliferation, morphology, protein expression of sex hormone receptors, fibrotic markers, proteoglycans, and gonadotropin signaling pathway members

STUDY TYPE

other

SPECIALTY

ophthalmology

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10726429

Selective Modulation of the Keratoconic Stromal Microenvironment by FSH and LH

The American Journal of Pathology

READ THE FULL PAPER

ABSTRACT

Keratoconus (KC) affects the corneal structure, with thinning and bulging outward into a conelike shape. Irregular astigmatism and decreased visual acuity appear during puberty and progress into the mid-30s, with unpredictable disease severity. The cause of KC is recognized as multifactorial, but remains poorly understood. Hormone imbalances are a significant modulator of the onset of KC. This study sought to investigate the role of gonadotropins, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in KC, using a three-dimensional, self-assembled matrix in vitro model. Healthy corneal fibroblasts and human KC cells in the corneal stroma were isolated, cultured, and stimulated with stable vitamin C to promote extracellular matrix assembly. Cultures were further stimulated with 2.5 or 10 mIU/mL FSH and 5 or 35 mIU/mL LH. Samples were evaluated for cell proliferation and morphology via BrdU assay and imaging; protein expression was assessed via Western blot analysis. Proliferation was significantly greater in human KC cells compared to healthy corneal fibroblasts with LH stimulation, but no changes were found with FSH stimulation. Additionally, in sex hormone receptors, fibrotic markers, proteoglycans, and members of the gonadotropin signaling pathway were significantly changed, largely driven by exogenous LH. The impact of exogenous FSH/LH in the KC stromal microenvironment was demonstrated. These results highlight the need to further examine the role of FSH/LH in KC and in human corneal homeostasis.

CITATION EXPORT

Paulina Escandon, Sarah E. Nicholas, Brenda Vasini et al.. Selective Modulation of the Keratoconic Stromal Microenvironment by FSH and LH. The American Journal of Pathology. (2023). https://doi.org/10.1016/j.ajpath.2023.02.002

AUTHORS

7 · 4 CENTRES

Paulina Escandon, Sarah E. Nicholas, Brenda Vasini, Rebecca L. Cunningham, David A. Murphy, Kamran M. Riaz, Dimitrios Karamichos

∗North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, Texas
†Department of Pharmaceutical Sciences, University of North Texas Health Science Center, Fort Worth, Texas
‡Department of Ophthalmology, Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
§Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Texas