Degeneration and Regeneration of Corneal Nerves in Response to HSV-1 Infection

作者：Ana J. Chucair‐Elliott, Min Zheng, Daniel J.J. Carr · 发表于：Investigative Ophthalmology & Visual Science · 年份：2015 · DOI：10.1167/iovs.14-15596 · 被引用次数：102 · 研究领域：Ocular Surface and Contact Lens、Corneal Surgery and Treatments、Retinal Development and Disorders

PURPOSE: Herpes simplex virus type 1 (HSV-1) infection is one cause of neurotrophic keratitis, characterized by decreases in corneal sensation, blink reflex, and tear secretion as consequence of damage to the sensory fibers innervating the cornea. Our aim was to characterize changes in the corneal nerve network and its function in response to HSV-1 infection. METHODS: C57BL/6J mice were infected with HSV-1 or left uninfected. Corneas were harvested at predetermined times post infection (pi) and assessed for β III tubulin, substance P, calcitonin gene-related peptide, and neurofilament H staining by immunohistochemistry (IHC). Corneal sensitivity was evaluated using a Cochet-Bonnet esthesiometer. Expression of genes associated with nerve repair was determined in corneas by real time RT-PCR, Western blotting, and IHC. Semaphorin 7A (SEMA 7A) neutralizing antibody or isotype control was subconjunctivally administered to infected mice. RESULTS: The area of cornea occupied by β III tubulin immunoreactivity and sensitivity significantly decreased by day 8 pi. Modified reinnervation was observed by day 30 pi without recovery of corneal sensation. Sensory fibers were lost by day 8 pi and were still absent or abnormal at day 30 pi. Expression of SEMA 7A increased at day 8 pi, localizing to corneal epithelial cells. Neutralization of SEMA 7A resulted in defective reinnervation and lower corneal sensitivity. CONCLUSIONS: Corneal sensory nerves were lost, consistent with loss of corneal ...