An Engineered Human Fibroblast Growth Factor-1 Derivative, TTHX1114, Ameliorates Short-term Corneal Nitrogen Mustard...

Area of Science:

• Ophthalmology and Regenerative Medicine
• Toxicology and Chemical Warfare Defense

Background:

• Nitrogen mustard (NM) causes severe epithelial lesions in the cornea.
• Fibroblast growth factor (FGF)-1 plays a role in corneal healing.
• Developing effective anti-vesicant therapies is crucial for treating chemical injuries.

Purpose of the Study:

• To evaluate the protective and regenerative efficacy of a modified human fibroblast growth factor (FGF)-1 derivative (TTHX1114) against nitrogen mustard (NM)-induced corneal epithelial damage.
• To assess the potential of TTHX1114 as a therapeutic agent for vesicant exposure.

Main Methods:

• Organ cultures of rabbit corneas were exposed to NM and treated with TTHX1114.
• Histopathology, 5-ethynyl-2'-deoxyuridine (EdU) incorporation for proliferation, and immunofluorescence for FGF-1 and ADAM-17 were used for assessment.
• Corneas were cultured for up to 14 days post-exposure.

Main Results:

• NM exposure led to near-complete epithelial loss by day 6, which significantly regenerated by day 14.
• Continuous TTHX1114 treatment maintained epithelial levels similar to day 2 post-exposure, significantly reducing NM-induced damage.
• TTHX1114 stimulated a strong proliferative response in corneal epithelial cells, while stromal keratocyte loss was unaffected. Native FGF-1 levels decreased rapidly after NM exposure.

Conclusions:

• TTHX1114 demonstrates significant protective effects against NM-induced corneal epithelial damage.
• The compound likely acts by providing NM-resistant trophic support and promoting epithelial cell regeneration.
• These findings support the potential of TTHX1114 as a valuable therapeutic for anti-vesicant applications.