Proliferation of Human Corneal Endothelia in Organ Culture Stimulated by Wounding and the Engineered Human Fibroblast Growth Factor 1 Derivative TTHX1114
| Autor: | Ralph A. Bradshaw, Jennifer Jenkins-Eveleth, Jessica Weant, Sarah Pizzuto, David Eveleth |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male 0301 basic medicine endothelium Endothelium Population FGF1 Protein Engineering Organ culture Fibroblast growth factor Cell junction 03 medical and health sciences Organ Culture Techniques 0302 clinical medicine cornea growth factors medicine Humans Pharmacology (medical) Progenitor cell education Aged Cell Proliferation Pharmacology Wound Healing education.field_of_study Chemistry Endothelium Corneal Fuchs endothelial corneal dystrophy Contact inhibition Original Articles Middle Aged Cell biology Endothelial stem cell Ophthalmology 030104 developmental biology medicine.anatomical_structure cardiovascular system 030221 ophthalmology & optometry Fibroblast Growth Factor 1 Female |
| Zdroj: | Journal of Ocular Pharmacology and Therapeutics |
| ISSN: | 1557-7732 1080-7683 |
| DOI: | 10.1089/jop.2019.0119 |
| Popis: | Purpose: Corneal endothelial dystrophies are characterized by endothelial cell loss and dysfunction. Recent evidence suggests that corneal endothelial cells (CECs) can regenerate although they do not do so under normal conditions. This work sought to test whether CECs can be stimulated to proliferate in organ culture by wounding and/or by treatment with the engineered human fibroblast growth factor 1 (FGF1) derivative TTHX1114. Methods: Human donor corneas obtained from eye banks were maintained in organ culture in the presence or absence of TTHX1114. Wounds in the corneas were created by quartering the corneas. The CEC monolayer was identified as a regular layer by Hoechst staining of the nuclear DNA with cell outlines delineated by immunohistochemical identification of ZO-1. Nuclei and nuclei incorporating 5-ethynyl-2′-deoxyuridine (EdU) were counted using ImageJ. Results: CECs in normal corneas in undisturbed monolayers had low, but measurable, rates of proliferation. CECs at the edge of a wound had higher rates of proliferation, probably due to the release of contact inhibition. TTHX1114 increased proliferation at wound edges. After 7 days of culture, proliferating CECs formed contiguous groups of labeled cells that did not migrate away from one another. TTHX1114-treated cells, including the EdU labeled proliferating cells, retained normal morphology, including cell/cell junction ZO-1 staining. Conclusions: Proliferation of CECs in organ-cultured corneas is low, but can be stimulated by wounding or by the administration of TTHX1114 with the effects of each being additive. The CEC monolayer appears to have a population of progenitor cells that are susceptible to stimulation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|