Abstract
Purpose: :
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.
Methods: :
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.
Results: :
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.
Conclusions: :
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 .
Keywords: wound healing • inflammation • cornea: stroma and keratocytes