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Ophthalmic combination of SurR9-C84A and trichostatin-A targeting molecular pathogenesis of alkali burn

Roy, Kislay, Sriramoju, Bhasker, Kanwar, Rupinder K. and Kanwar, Jagat R. 2016, Ophthalmic combination of SurR9-C84A and trichostatin-A targeting molecular pathogenesis of alkali burn, Frontiers in Pharmacology, vol. 7, pp. 1-14, doi: 10.3389/fphar.2016.00226.

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Title Ophthalmic combination of SurR9-C84A and trichostatin-A targeting molecular pathogenesis of alkali burn
Author(s) Roy, Kislay
Sriramoju, Bhasker
Kanwar, Rupinder K.
Kanwar, Jagat R.
Journal name Frontiers in Pharmacology
Volume number 7
Start page 1
End page 14
Total pages 14
Publisher Frontiers Media
Place of publication Lausanne, Switzerland
Publication date 2016-07-28
ISSN 1663-9812
Keyword(s) TGF-β
alkali burn
clathrin
claudin
cytokines
survivin
trichostatin-A
α-SMA
Science & Technology
Life Sciences & Biomedicine
Pharmacology & Pharmacy
TGF-beta
alpha-SMA
MYOFIBROBLAST DIFFERENTIATION
HISTONE DEACETYLASE
CORNEAL EPITHELIUM
OCULAR SURFACE
RABBIT CORNEA
MITOMYCIN-C
EXPRESSION
CELLS
Summary BACKGROUND: Alkali burn is a frequently occurring ocular injury that resembles ocular inflammation caused by eye allergies, infection, and refractive surgeries.
METHODS: We investigated the synergistic regenerative potential of dominant negative survivin mutant (SurR9-C84A) and histone deacetylase (HDAC) inhibitor trichostatin-A (TSA) against alkali burn and corneal haze using human keratocytes and rabbit alkali burn model (Female New Zealand white rabbits).
RESULTS: Combination of SurR9-C84A and TSA suppressed levels of transforming growth factor (TGF)-β, alpha smooth-muscle actin (α-SMA), fibronectin and HDAC1, leading to apoptosis in myofibroblast cells and, showed the potential to clear the corneal haze. An insult with 0.5 N NaOH for 1 min led to neutrophils infiltration and formation of large vacuoles in the stroma. Treatments with TSA and SurR9-C84A for 40 min led to improvement in the conjunctival and corneal tissue integrity, marked by an increase in clathrin, and claudin expressions. An increase in TGF-β and endogenous survivin confirmed wound healing and cell proliferation in rabbit cornea. The blood analysis revealed a substantial decrease in the RBC, WBC, platelets, or the hemoglobin content post alkali burn. The cytokine array analysis revealed that NaOH induced expressions of IL-1α and MMP-9, which were found to be significantly downregulated (1.8 and 11.5 fold respectively) by the combinatorial treatment of SurR9-C84A and TSA.
CONCLUSION: Our results confirmed that combination of SurR9-C84A with TSA worked in synergy to heal ocular injury and inflammations due to alkali burn and led to the regeneration of ocular tissue by increasing clathrin, claudin, survivin, and TGF-β and reversal of alkali burn by suppressing IL-1α and MMP-9 without inducing haze.
Language eng
DOI 10.3389/fphar.2016.00226
Field of Research 111303 Vision Science
1115 Pharmacology And Pharmaceutical Sciences
Socio Economic Objective 920107 Hearing
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, Roy, Sriramoju, Kanwar and Kanwar
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30087411

Document type: Journal Article
Collections: School of Medicine
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Created: Thu, 13 Oct 2016, 13:57:13 EST

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.