July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Role of Neuropilin-1 in Impaired Sensory Nerve Regeneration and Wound Healing in the Diabetic Mouse Cornea
Author Affiliations & Notes
  • Patrick Shean-Young Lee
    Ophthalmology, Wayne State University School of Medicine, Detroit, Michigan, United States
  • Fushin X Yu
    Ophthalmology, Wayne State University School of Medicine, Detroit, Michigan, United States
  • Footnotes
    Commercial Relationships   Patrick Lee, None; Fushin Yu, None
  • Footnotes
    Support  R01EY10869, EY17960, EY025923, EY004068
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3214. doi:
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      Patrick Shean-Young Lee, Fushin X Yu; Role of Neuropilin-1 in Impaired Sensory Nerve Regeneration and Wound Healing in the Diabetic Mouse Cornea. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3214.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Since its initial discovery as an axonal guidance molecule in the nervous system, Neuropilin-1 has been identified as a receptor that mediates diverse functions such as immune cell signaling and axon guidance. This study sought to investigate the role of Neuropilin-1 in epithelium innervation in homeostatic corneas and re-innervation in post-wound corneas of normal and diabetic mice.

Methods : Corneas were wounded by debridement and allowed to heal in vivo. Fluorescein staining was used to assess wound size after debridement. Functional antibodies for receptor blockade were subconjunctivally injected prior to epithelium-wounding. Sensory nerve fibers/endings were assessed by whole mount confocal microscopy. Dendritic cell depletion was accomplished via Diphtheria toxin subconjunctival injections in CD11c-DTR mice.

Results : Corneal epithelial expression of Nrp1 was significantly higher in unwounded diabetic mice than in normal mice. Wounding suppressed Nrp1 expression in diabetic corneas and exhibited no effects on normal corneas. Nrp1 blockade by subconjunctival antibody injections in wounded diabetic mice resulted in a decrease in the rate of wound healing but an increase in regenerating nerve fibers. Nonwounded diabetic corneas contained significantly fewer CD11c-positive cells compared to nonwounded normal corneas. Depletion of CD11c-positive cells in nonwounded normal corneas resulted in upregulation of Nrp1 expression.

Conclusions : Epithelium-expressed Nrp1 plays a role in the cornea, with opposing roles in the regeneration of sensory nerve fibers/endings and the epithelium. Diabetes-induced decrease in residential CD11c-positive cells may play a role in upregulation of corneal epithelial Nrp1 expression.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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