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An Engineered Human Fibroblast Growth Factor-1 Derivative, TTHX1114, Ameliorates Short-term Corneal Nitrogen Mustard Injury in Rabbit Organ Cultures

An Engineered Human Fibroblast Growth Factor-1 Derivative, TTHX1114, Ameliorates Short-term Corneal Nitrogen Mustard Injury in Rabbit Organ Cultures

David D Eveleth, Jennifer J Eveleth, Amuthakannan Subramaniam, Rita Hahn, Peihong Zhou, Marion K Gordon, Ralph A Bradshaw

Invest Ophthalmol Vis Sci. 2018 Sep 4;59(11):4720-4730.

PMID: 30267094

Abstract:

Purpose:
Organ cultures of rabbit corneas have been used to ascertain the effectiveness of a human fibroblast growth factor (FGF)-1 derivative (TTHX1114), lacking cysteine residues, to protect against and/or repair epithelial lesions following exposure to nitrogen mustard (NM).
Methods:
Rabbit corneas were exposed to NM and cultured for up to 14 days, with or without drug (TTHX1114). At specified times, tissue was examined by histopathology and graded by a novel composite scale. Proliferation was measured by 5-ethynyl-2'-deoxyuridine (EdU) incorporation, and the expression of native FGF-1 and ADAM-17 after NM exposure was determined by immunofluorescence.
Results:
Rabbit corneas, exposed to a single dose of NM, showed a nearly complete loss of epithelial cells by day 6 but were significantly regenerated by day 14. When treated continuously with TTHX1114 following vesicant exposure, the losses remained at day 2 levels. The loss of keratocytes in the stroma was not affected by TTHX1114. EdU incorporation over the same time course showed a steady increase in tissue that had not been treated with TTHX1114, while corneas that were treated with the drug showed a higher percent incorporation initially, which then decreased, indicating the strong proliferative response to TTHX1114. ADAM-17 was not significantly altered by TTHX1114 treatment. Corneal epithelial FGF-1 disappeared after only 1 day following exposure to NM.
Conclusions:
TTHX1114 is protective against NM-induced damage of the corneal epithelium, possibly by supplying an NM-resistant source of trophic support and by stimulating regeneration of new epithelial cells. These responses underscore the potential value of TTHX1114 as an anti-vesicant therapeutic.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248581	Fibroblast Growth Factor-Acidic human			Price

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