June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Proliferation of human corneal endothelia in organ culture stimulated by engineered human fibroblast growth factor 1 (FGF1) derivative TTHX1114
Author Affiliations & Notes
  • Sarah Pizzuto
    Trefoil Therapeutics, Inc., San Diego, California, United States
  • David Eveleth
    Trefoil Therapeutics, Inc., San Diego, California, United States
  • Jessica Weant
    Trefoil Therapeutics, Inc., San Diego, California, United States
  • Jennifer Jenkins-Eveleth
    Trefoil Therapeutics, Inc., San Diego, California, United States
  • Ralph A. Bradshaw
    Trefoil Therapeutics, Inc., San Diego, California, United States
    Dept. of Physiology and Biophysics, University of California, Irvine, Irvine, California, United States
  • Footnotes
    Commercial Relationships   Sarah Pizzuto, Trefoil Therapeutics, Inc. (E); David Eveleth, Trefoil Therapeutics (I), Trefoil Therapeutics (E), Trefoil Therapeutics (P), Trefoil Therapeutics (S); Jessica Weant, Trefoil Therapeutics (I), Trefoil Therapeutics (E); Jennifer Jenkins-Eveleth, Trefoil Therapeutics (E), Trefoil Therapeutics (P); Ralph Bradshaw, Trefoil Therapeutics (I), Trefoil Therapeutics (E), Trefoil Therapeutics (C), Trefoil Therapeutics (P), Trefoil Therapeutics (S)
  • Footnotes
    Support  NIH NCATS TRND CRADA# 2016-04
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 3263. doi:
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    • Get Citation

      Sarah Pizzuto, David Eveleth, Jessica Weant, Jennifer Jenkins-Eveleth, Ralph A. Bradshaw; Proliferation of human corneal endothelia in organ culture stimulated by engineered human fibroblast growth factor 1 (FGF1) derivative TTHX1114. Invest. Ophthalmol. Vis. Sci. 2020;61(7):3263.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Corneal endothelial dystrophies result from 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 FGF1 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 have low, but measurable, rates of proliferation. CECs at the edge of a wound have higher rates of proliferation. TTHX1114 increases proliferation both in the undisturbed monolayer and at wound edges. After 7 days of culture, proliferating CECs form contiguous groups of labeled cells that do not migrate away from one another. TTHX1114 treated cells, including the EdU proliferating cells, retain normal morphology including cell-cell junction ZO-1 staining. Proliferation rates are generally lower in corneas from female donors than male donors.

Conclusions : Proliferation of CECs in organ cultured corneas is low but can be stimulated by wounding or with 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. TTHX1114 may be useful in stimulating CEC proliferation in endothelial dystrophies.

This is a 2020 ARVO Annual Meeting abstract.

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