Abstract
Purpose :
To determine if transient receptor potential vanilloid 4 (TRPV4), TRPV1-related component, contributes to epithelial wound healing in a mouse cornea. Growth factor expression pattern was also evaluated. TRP family consists of groups of TRPV, ankyrin 1 (TRPA1) or melastatin (TRPM). We previously reported the involvement of TRPV1 and TRPA1 in corneal epithelial wound healing in mice (IOVS 2014, ARVO 2015).
Methods :
Imunohistochemistry was carried out to examine the expression opattern of TRPV4 in mouse cornea. Time dependent closure of a 2.0 mm diameter central corneal epithelial debridement was monitored in the right eyes of C57BL/6 (wild type, WT, n =61) and TRPV4-null (KO, n =61) mice for up to 36 h using fluorescein green staining. BrdU-labeling in WT and KO mice evaluated proliferative activity during healing. RT-PCR analyzed interleukin 6 (IL-6), substance P (SP) calcitonin gene-related peptide (CGRP), nerve growth factor (NGF) and transforming growth factor b1 (TGFb1) gene expression levels.
Results :
TRPV4 was detected in the basal cells of the corneal epithelium. The open wound area in the TRPV4 KO mice at 18 and 24 hr was 1.6-fold and 7.34-fold bigger than in the WT counterpart, respectively. BrdU-labeled cells were fewer in the KO healing epithelium than in the WT counterpart at 24 and 36 hr (p<0.05). Increases in CGRP, NGF and TGFb1 gene expression were smaller than those in the WT counterpart (p<0.05) whereas increases in IL-6 and SP were unaffected by the loss of TRPV4 function.
Conclusions :
TRPV4 mediated signaling contributes to increases in CGRP, NGF and TGFb1 gene expression and repair of a corneal epithelial debridement in mice.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.