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Harumitsu Hirata, Pengxia Wan, Victor H Guaiquil, Mark Rosenblatt; VEGF-B improves a functional recovery of the corneal nerves following corneal injury. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):717.
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© ARVO (1962-2015); The Authors (2016-present)
. Our previous study reported a remarkable ability of the growth factor, VEGF-B, to repair corneal nerves after experimental injury. The present study investigated the functional nature of healing of the corneal nerves using in vivo electrophysiology.
A total corneal epithelial debridement except the most peripheral (limbal) region was performed in male Sprague-Dawley rats, which was followed by sub-conjunctival injections of either VEGF-B or PBS. Three or 10 days after debridement, in vivo recordings were made from trigeminal ganglion neurons innervating the cornea in isoflurane-anesthetized animals. A variety of somatic and chemical stimuli were applied to the cornea to characterize their receptive field (RF) properties and to determine the types and the extent of the functional recovery from injury.
Three days after the debridement, we found more RFs localized on the central part of the cornea among VEGF-B than PBS treated animals, consistent with our prior findings that VEGF-B accelerates the regeneration of corneal sub-basal nerves. Furthermore, ten days after the debridement, RF characteristics of neurons in VEGF treated groups were consistent with those previously observed in normal animals. In contrast, some neurons in PBS treated groups showed inconsistent RF properties not seen in the VEGF-B treated or uninjured groups, including a lack of normal heat response in a special class of neurons exquisitely sensitive to cooling. Additionally, neurons from the PBS group displayed a response to capsaicin, a TRPV1 agonist, that was much stronger than that observed in uninjured neurons. Finally, in both VEGF-B and PBS groups, the responses to drying of the cornea (dry responses) were generally smaller than the normal animals. These data suggest that the corneal nerve function was more profoundly impaired in PBS treated neurons than in neurons which were treated with VEGF-B.
Our results demonstrated that VEGF-B facilitated a functional recovery of many of the RF properties of the corneal nerves. The more rapid restoration of both innervation and corneal sensation using VEGF-B, provides a possible new target for treating corneal injury and neurotrophic diseases.
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