Topical Ophthalmic Formulation of Trichostatin A and SurR9-C84A for Quick Recovery Post-alkali Burn of Corneal Haze

Frontiers in Pharmacology
Kislay RoyJagat R Kanwar

Abstract

Alkali burn injury is a true ocular emergency of the conjunctiva and cornea that requires immediate precision. Lack of an immediate therapy can lead to a substantial damage in the ocular surface and anterior segment further causing visual impairment and disfigurement. We explored the regenerative capability of dominant negative survivin protein (SurR9-C84A) and histone deacetylase inhibitor trichostatin-A (TSA) in vivo, in a rat alkali burn model. A topical insult in rat eyes with NaOH led to degradation of the conjunctival and corneal epithelium. The integrity of the conjunctival and corneal tissue was increased by TSA and SurR9-C84A by improving the clathrin and claudin expressions. Wound healing was initiated by an increase in TGF-beta-1 and, increased endogenous survivin which inhibited apoptosis post-TSA and SurR9-C84A treatments. Protein expressions of fibronectin and alpha-integrin 5 were found to increase promoting corneal integrity. The cytokine analysis confirmed increased expressions of IL-1beta, IL-6, IL-12, IL-13, IFN-gamma, TNF-alpha, GMCSF, Rantes, and MMP-2 in injured cornea, which were found to be significantly downregulated by the combined treatment of SurR9-C84A and TSA. The ocular and systemic pharmacokineti...Continue Reading

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Citations

Jul 22, 2018·Journal of Molecular Endocrinology·Carla A PiccinatoPhilippa T K Saunders
Jul 19, 2018·Development and Psychopathology·Jerome Kagan
Dec 1, 2019·Chemical Biology & Drug Design·Nilüfer BayrakAmaç Fatih Tuyun

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Methods Mentioned

BETA
ELISArray
Assay
ELISA
Alpha-SMA
confocal microscopy
PCR
acetylation

Software Mentioned

Graphpad
image J
Living Image

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