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Yuka Okada, Peter S. Reinach, Kumi Shirai, Ai Kitano, Masayasu Miyajima, Shizuya Saika; Effects Of Loss Of TRPV4 On The Inflammation And Scarring Of An Alkali-burned Cornea In Mice. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2022.
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© ARVO (1962-2015); The Authors (2016-present)
We reported that in mice transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankrin 1 (TRPA1) gene ablation markedly improved the corneal wound healing response to alkali burning (ARVO, 2009, 2010). Currently, we determined if transient receptor potential vanilloid 4 (TRPV4) gene ablation also affects inflammation and scarring severity during wound healing of alkali-burned mice corneas.
1) Immunohistochemistry probed for TRPV4 protein expression in mice corneas . 2) Three microliters of 1 N NaOH were applied under general anesthesia to the right eye of 6-8 week old TRPV4(-/-)(KO) (n=44) or TRPV4(+/+) (WT) (n=44) mice to produce an ocular surface alkali burn. The eyes were processed for histology/immunohistochemistry or real time RT-PCR.
1) TRPV4 protein expression was detected in the corneal epithelium. 2) Stroma of the KO healing corneas were more transparent as compared with those of WT mice at 5 to 20 days post-alkali burn. Hematoxylin-eosin histological staining indicated more marked inflammation in the thickened stroma in the corneas of WT mice. Immunohistochemical and real time RT-PCR examinations showed less α-smooth muscle actin, F4/80, myeloperoxidase, TGFβ1, Collagen1a1 and MCP-1 expression in the cornea of KO mice after alkali burn.
TRPV4 is a calcium-permeable channel activated by extracellular hypotonicity, polyunsaturated fatty acids, phorbol esters, and heat. To the best of our knowledge, this report shows for the first time that in TRPV4 KO mice, the corneal wound healing response to an alkali burn has an improved outcome since there is less inflammation and scarring than in the WT counterpart.
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