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.