June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
TTHX1114 Protects Primary Rabbit Corneal Endothelial Cells from Oxidative Stress
Author Affiliations & Notes
  • Anna Stuhlfire
    Trefoil Therapeutics, San Diego, California, United States
  • Lindsey Myers
    Trefoil Therapeutics, San Diego, California, United States
  • Grace Duffey
    Trefoil Therapeutics, San Diego, California, United States
  • Jessica Weant
    Trefoil Therapeutics, San Diego, California, United States
  • David Eveleth
    Trefoil Therapeutics, San Diego, California, United States
  • Footnotes
    Commercial Relationships   Anna Stuhlfire Trefoil Therapeutics, Code E (Employment), Trefoil Therapeutics, Code I (Personal Financial Interest); Lindsey Myers Trefoil Therapeutics, Code E (Employment), Trefoil Therapeutics, Code I (Personal Financial Interest); Grace Duffey Trefoil Therapeutics, Code E (Employment), Trefoil Therapeutics, Code I (Personal Financial Interest); Jessica Weant Trefoil Therapeutics, Code E (Employment), Trefoil Therapeutics, Code I (Personal Financial Interest); David Eveleth Trefoil Therapeutics, Code I (Personal Financial Interest), Trefoil Therapeutics, Code O (Owner)
  • Footnotes
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Investigative Ophthalmology & Visual Science June 2023, Vol.64, 621. doi:
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      Anna Stuhlfire, Lindsey Myers, Grace Duffey, Jessica Weant, David Eveleth; TTHX1114 Protects Primary Rabbit Corneal Endothelial Cells from Oxidative Stress. Invest. Ophthalmol. Vis. Sci. 2023;64(8):621.

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

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Abstract

Purpose : Oxidative stress is closely tied to Fuchs’ Endothelial Corneal Dystrophy (FECD) and can cause complications during phacoemulsification and aspiration (PEA) in cataract surgery. Protecting the corneal endothelium from further damage due to oxidative stress would prove beneficial for FECD patients and cataract patients. The purpose of this study was to investigate the protective effects of TTHX1114, a synthetic analog of FGF1, on the viability of rabbit corneal endothelial cells exposed to oxidative stress.

Methods : Primary cultures of rabbit corneal endothelial cells were insulted with 10 μM or 50 μM tert-butyl hydroperoxide (tBHP) to induce mild and harsh oxidative stress. The cultures were organized into cohorts which received a 24-hour TTHX1114 pre-treatment before insult, a 24-hour or 48-hour post-treatment after insult, or both a pre- and post-treatment. After each dosing schedule, cell viability was measured via MTT assay.

Results : In the cultures that received a 10 μM tBHP insult we found either a TTHX1114 pre-treatment or post-treatment were sufficient to protect cell viability with no significant difference (p > 0.05) between +24-hour pre-treatment +48-hour post-treatment and +48-hour post-treatment alone. In cultures that received a 50 μM tBHP insult cell viability was significantly (p < 0.0001) protected in the cohort that received a 24-hour pre-treatment compared to each paired condition that received only a post-treatment. There was no significant difference (p > 0.05) between +24-hour pre-treatment +48-hour post-treatment and the corresponding growth media no insult control in both the 10 μM and 50 μM tBHP insult conditions indicating that pre- and post-treatment yielded metabolically stable cells similar to the growth media only control.

Conclusions : In cell culture, TTHX1114 protects rabbit corneal endothelial cell viability against tBHP induced oxidative stress. This gives support for TTHX1114 treatments as a promising approach in the clinic for protecting FECD patients or cataract patients undergoing PEA from corneal endothelial damage due to oxidative stress.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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