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Y. Okada, P. S. Reinach, K. Shirai, A. Kitano, M. Miyajima, S. Saika; Trpa1 Gene Ablation in Mice Improves Corneal Wound Healing Response to Injury. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2496.
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© ARVO (1962-2015); The Authors (2016-present)
We reported that in mice transient receptor potential vanilloid 1 (TRPV1), gene ablation markedly improved the corneal wound healing response to alkali burning. This phenotype is recapitulated by repeated treatment of wild-type mice with TRPV1 antagonists subsequent to injury. (ARVO, 2009). Currently, we determined if transient receptor potential ankrin 1 (TRPA1) gene ablation or TRPA1 antagonist treatment also affects inflammation and scarring severity during wound healing of alkali-burned mice corneas.
1) Immunohistochemistry probed for TRPA1 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 TRPA1(-/-)(KO) (n=10) or TRPA1(+/+) (WT) (n=10) mice to produce an ocular surface alkali burn. 3) Three microliters of 1 N NaOH was applied to the right eye of WT (n=24) mice to produce an ocular surface alkali burn under general anesthesia. The mice received intraperitoneal injections of TRPA1 receptor antagonist HC-030031 (100 mg/kg, daily) or its vehicle. Eyes were histologically examined at 5, 10, 20 days after alkali burn. Myofibroblast transdifferentiation and inflammatory cell infiltration into the wounds were assessed based on immunohistochemical staining obtained with antibodies against either alpha-SMA, F4/80 (macrophage) or myeloperoxidase (MPO) (neutrophil).
1) TRPA1 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 cornea of WT mice. Immunohistochemical staining showed less alpha-SMA, F4/80 and MPO in the cornea of KO mice after alkali burn. 3) Systemic HC-030031 suppressed inflammation and scarring in WT mice.
TRPA1 is an irritant-sensing ion channel. Loss of TRPA1 in mice reduces inflammation and scarring during the wound healing in cornea following an alkali burn.
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