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Topical ophthalmic formulation of Trichostatin A and SurR9-C84A for quick recovery post-alkali burn of corneal haze

Roy, Kislay, Cheung, Chun Hei Antonio, Kanwar, Rupinder K., Sandhir, Rajat and Kanwar, Jagat R. 2017, Topical ophthalmic formulation of Trichostatin A and SurR9-C84A for quick recovery post-alkali burn of corneal haze, Experimental pharmacology and drug discovery, vol. 8, pp. 1-15, doi: 10.3389/fphar.2017.00223.

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Title Topical ophthalmic formulation of Trichostatin A and SurR9-C84A for quick recovery post-alkali burn of corneal haze
Author(s) Roy, Kislay
Cheung, Chun Hei Antonio
Kanwar, Rupinder K.
Sandhir, Rajat
Kanwar, Jagat R.ORCID iD for Kanwar, Jagat R. orcid.org/0000-0003-3728-9568
Journal name Experimental pharmacology and drug discovery
Volume number 8
Article ID 223
Start page 1
End page 15
Total pages 15
Publisher Frontiers
Place of publication Lausanne, Switzerland
Publication date 2017-05
ISSN 1663-9812
Keyword(s) cytokines
haze
scarring
survivin
trichostatin-A
wound healing
Science & Technology
Life Sciences & Biomedicine
Pharmacology & Pharmacy
EPITHELIAL-CELLS
EXPRESSION
NEOVASCULARIZATION
INTERLEUKIN-1
INFLAMMATION
COLLAGEN
THERAPY
INJURY
VIVO
DNA
Summary 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 pharmacokinetic (PK) parameters were measured post-topical ocular administration of TSA and SurR9-C84A. The SurR9-C84A and TSA sustained relatively longer in the cornea, conjunctiva, and aqueous humor than in the tear fluid and plasma. Our results confirmed that a combination of TSA with SurR9-C8A worked in synergy and showed a promising healing and anti-inflammatory effect in a very short time against alkali burn. Therefore, a combination of TSA and SurR9-C84A can fulfill the need for an immediate response to wound healing in alkali burnt cornea. We also synthesized ultra-small chitosan nanoparticles (USC-NPs) targeted with alpha-SMA antibodies that can be used for delivery of TSA and SurR9-C84A specifically to the ocular burn site.
Language eng
DOI 10.3389/fphar.2017.00223
Field of Research 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
1115 Pharmacology And Pharmaceutical Sciences
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2017, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30100533

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
Open Access Collection
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.