June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Accelerated regeneration of corneal endothelium after Descemet’s stripping mediated by the engineered fibroblast growth factor TTHX1114
Author Affiliations & Notes
  • Sarah Pizzuto
    Trefoil Therapeutics, San Diego, California, United States
  • Jessica Weant
    Trefoil Therapeutics, San Diego, California, United States
  • Natalie A Afshari
    University of California at San Diego Department of Ophthalmology at the Shiley Eye Institute, La Jolla, California, United States
  • David Eveleth
    Trefoil Therapeutics, San Diego, California, United States
  • Footnotes
    Commercial Relationships   Sarah Pizzuto, Trefoil Therapeutics (E), Trefoil Therapeutics (I); Jessica Weant, Trefoil Therapeutics (E), Trefoil Therapeutics (I); Natalie Afshari, Trefoil Therapeutics (I); David Eveleth, Trefoil Therapeutics (P), Trefoil Therapeutics (E), Trefoil Therapeutics (I)
  • Footnotes
    Support  NIH NCATS TRND CRADA# 2016-04
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 797. doi:
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    • Get Citation

      Sarah Pizzuto, Jessica Weant, Natalie A Afshari, David Eveleth; Accelerated regeneration of corneal endothelium after Descemet’s stripping mediated by the engineered fibroblast growth factor TTHX1114. Invest. Ophthalmol. Vis. Sci. 2021;62(8):797.

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

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Purpose : Corneal endothelial dystrophy is currently being experimentally treated with limited descemet’s stripping without transplantation. This work sought to test whether the regeneration of the endothelial layer after Descemet’s stripping could be accelerated in corneal organ culture by treatment with an engineered form of FGF1 (TTHX1114).

Methods : Human corneas obtained from eye banks were maintained in organ culture. Descemet’s stripping was performed to remove the central 4mm of endothelial cells with underlying Descemet’s membrane. Corneas were then incubated in the presence or absence of TTHX1114 and the recovery of the endothelial layer evaluated by Trypan Blue and Alizarin Red staining. Lesion healing was quantitated using ImageJ. Invasion and proliferation of endothelial cells in the lesion area were evaluated by EdU incorporation and immunostaining with ZO-1.

Results : In both normal corneas and in corneas with guttae noted by the eye bank, healing of the stripped area without treatment was slow with about 30% of the stripped area healed at 14 days as judged by Trypan Blue. Healing in the presence of TTHX1114 was much more rapid, with 81% and 91% of the stripped area healed in normal and dystrophic corneas, respectively. Comparison of the lesion sizes between treated and control corneas was statistically significant (normal, p < 0.001, n=10 corneas per group; dystrophic, p < 0.001, n=11 corneas per group). In the healed areas of the treated corneas, Alizarin Red staining and ZO-1 staining revealed endothelial cells with defined ZO-1 rich cell borders covering parts of the lesion area. The endothelial cells covering the lesion area incorporate EdU indicating that they are actively proliferating.

Conclusions : The healing of Descemet’s stripping lesions can be accelerated by engineered FGF1 in human corneas ex vivo in both normal corneas and corneas with signs of endothelial dystrophy.

This is a 2021 ARVO Annual Meeting abstract.


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