Impairment of corneal epithelial wound healing in a TRPV1-deficient mouse.
OBJECTIVE
To examine whether the absence or blockage of an ion channel receptor, transient receptor potential vanilloid subtype 1 (TRPV1), affects the healing of an epithelial injury using an experimental model of an epithelial defect in animal cornea.


METHODS
The expression of TRPV1 in the corneal epithelium was examined using immunohistochemistry in mice and rats. The migration of the corneal epithelium was examined in epithelium-debrided rat cornea in organ culture in the presence or absence of a TRPV1 agonist or its antagonist. Epithelial migration and cell proliferation following the debridement were examined in the cornea of a TRPV1-null mouse. Real-time RT-PCR was performed in samples of healing corneas to analyze the expression pattern of epithelial migration-related components (i.e., IL-6, substance P, and TGF-β1).


RESULTS
TRPV1 was detected mainly in the basal layer of mouse or rat corneal epithelium. Adding a TRPV1 receptor agonist to the culture medium enhanced epithelial healing in the rat cornea, and a TRPV1 antagonist retarded it in organ culture. The loss of TRPV1 did not affect the histology of the mouse cornea. In vivo analysis showed the loss of TRPV1-impaired re-epithelialization of the debrided area of the corneal epithelium by the suppression of both cell migration and proliferation. The lack of TRPV1 suppressed the expression of IL-6 and substance P but not of TGF-β1 in response to epithelial debridement in mice.


CONCLUSIONS
TRPV1 signal is required for the upregulation of IL-6 and substance P and the healing of debrided corneal epithelium in mice.
Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan.
Takayoshi
T
Sumioka
Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan.
Yuka
Y
Okada
Wenzhou Medical School , Department of Ophthalmology and Optometry, Wenzhou, People's Republic of China.
Peter S
PS
Reinach
Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan.
Kumi
K
Shirai
Laboratory Animal Center, Wakayama Medical University School of Medicine, Wakayama, Japan.
Masayasu
M
Miyajima
Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan.
Osamu
O
Yamanaka
Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan.
Shizuya
S
Saika
D000818:Animals; D049109:Cell Proliferation; D004195:Disease Models, Animal; D019573:Epithelium, Corneal / Q000293:injuries / Q000378:metabolism / Q000473:pathology*; D005131:Eye Injuries / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D012313:RNA / Q000235:genetics*; D050916:TRPV Cation Channels / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics*; D014945:Wound Healing / Q000235:genetics*
D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D012313:RNA
epithelium; interleukin 6; knockout mouse; organ culture; substance P; transient receptor potential vanilloid subtype 1; wound healing