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Y. Okada, S. Saika, K. Shirai, A. Kitano, M. Miyajima, P. S. Reinach; Effects of Loss of Trpv1 on the Inflammation After an Alkali-Burned Cornea in Mice. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3069.
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© ARVO (1962-2015); The Authors (2016-present)
The transient receptor potential protein vanilloid 1 isoform (TRPV1) is a nonselective cation channel expressed in the murine corneal epithelium. It can be activated by hypertonic stress, noxious heat or a decline in pH. We determined in mice if loss of TRPV1 function and pharmacological suppression of its activation improves the corneal wound healing response to alkali burning.
Three microliters of 1 N NaOH were applied to the right eyes of 6-8 week old TRPV1 (-/-) (KO) (n=38) or TRPV1 (+/+) (WT) (n=38) mice to produce an ocular surface burn under general anesthesia. Alternatively, WT mice received intraperitoneal injections of either a selective TRPV1 antagonist, SB366791 (500 microgram/Kg daily), JYL1421 (2 mg/Kg daily), or their vehicle prior to injury. Eyes were histologically examined at 1, 2,5,10 and 20 days after burning. Immunohistochemistry was done to detect myofibroblast formation based on alpha smooth muscle actin (-SMA) expression levels. F4/80 and myeloperoxidase (MPO) staining monitored macrophage and neutrophil infiltration.
At 10 and 20 days, the corneas of both the KO and antagonist-treated WT mice were more transparent than their non-treated WT counterpart. In some of the non-treated WT counterpart group, hemorrhaging and global perforation were seen. These poorer outcomes were associated with corneal thickening and stromal disorganization. Furthermore, WT mice had more -SMA, F4/80 and MPO corneal staining than their KO counterpart. Similar improvements to those seen in the KO group were observed in the TRPV1 antagonist injected group.
In the KO and antagonist-treated WT mice, closure is associated with far less corneal transluscence, much less inflammation, scar formation, no bleeding and perforation. This favorable outcome could mean that TRPV1 is a potential drug target for reducing the adverse effects of TRPV1 activation by injury .
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