Hosoon Choi1, Casie Phillips1, Joo Youn Oh2, Luke Potts3, Roxanne L Reger4, Darwin J Prockop4, Samuel Fulcher5. 1. a Department of Basic Research, Central Texas Veterans Research Foundation , Temple , Texas , USA. 2. b Department of Ophthalmology, Seoul National University Hospital , Seoul , Republic of Korea. 3. c Department of Ophthalmology and Surgery, Scott and White Eye Institute , Temple , Texas , USA. 4. d Institute for Regenerative Medicine, College of Medicine, Texas A&M University , College Station , Texas , USA. 5. e Department of Surgery, Central Texas Veterans Health Care System , Temple , Texas , United States of America.
Abstract
Purpose: To investigate the therapeutic efficacy of tumor necrosis factor (TNF)-α stimulated gene/protein 6 (TSG-6) in a rat model of corneal alkali injury. Methods: Corneal alkali injury was produced by placing an NaOH-soaked filter paper disk on the central cornea of the right eye of an anesthetized male Lewis (LEW/Crl) rat. Recombinant human TSG-6, or an equal volume of phosphate-buffered saline (PBS), was administered intravenously (IV), by anterior chamber (AC) injection, or as a topical drop. The affected eyes were photographed daily using a dissecting microscope and documented for clinical time course analysis of corneal opacification. Corneal tissue was excised at pre-determined therapeutic endpoints, with subsequent qRT-PCR or histological analyses. Results: The continuous monitoring of corneal alkali injury progression revealed TSG-6 treatments do not show sufficient effectiveness in vivo regardless of IV injection, AC injection, or topical application. Corneal opacification and neovascularization were not diminished, and gene expression was not impacted by these treatments. However, both IV and AC administration of TSG-6 significantly suppressed pro-inflammatory cytokines compared to PBS-treated eyes. Conclusion: We conclude that the therapeutic potential of TSG-6 is insufficient in a rat corneal alkali injury model.
Purpose: To investigate the therapeutic efficacy of tumor necrosis factor (TNF)-α stimulated gene/protein 6 (TSG-6) in a rat model of corneal alkali injury. Methods:Corneal alkali injury was produced by placing an NaOH-soaked filter paper disk on the central cornea of the right eye of an anesthetized male Lewis (LEW/Crl) rat. Recombinant humanTSG-6, or an equal volume of phosphate-buffered saline (PBS), was administered intravenously (IV), by anterior chamber (AC) injection, or as a topical drop. The affected eyes were photographed daily using a dissecting microscope and documented for clinical time course analysis of corneal opacification. Corneal tissue was excised at pre-determined therapeutic endpoints, with subsequent qRT-PCR or histological analyses. Results: The continuous monitoring of corneal alkali injury progression revealed TSG-6 treatments do not show sufficient effectiveness in vivo regardless of IV injection, AC injection, or topical application. Corneal opacification and neovascularization were not diminished, and gene expression was not impacted by these treatments. However, both IV and AC administration of TSG-6 significantly suppressed pro-inflammatory cytokines compared to PBS-treated eyes. Conclusion: We conclude that the therapeutic potential of TSG-6 is insufficient in a ratcorneal alkali injury model.
Authors: Kumar Abhiram Jha; Mickey Pentecost; Raji Lenin; Jordy Gentry; Lada Klaic; Nobel Del Mar; Anton Reiner; Chuan He Yang; Lawrence M Pfeffer; Nicolas Sohl; Rajashekhar Gangaraju Journal: Stem Cell Res Ther Date: 2019-11-05 Impact factor: 6.832