Abstract
Purpose :
Despite evidence has demonstrated impairment of endothelial function with diseases involving neurologic change, how corneal nerve impairment alters corneal endothelium remains unclear. The study seeks to evaluate the impact of trigeminal denervation on corneal endothelium.
Methods :
Corneal denervation of C57BL/6J mice was achieved by damaging the first branch of trigeminal nerve with stereotactic electrolysis. Corneal sensation and corneal nerve staining were performed to confirm the status of denervation. Corneal sensation was evaluated with corneal esthesiometer before denervation and on post-denervation day 1, 3, 7. Staining of corneal nerve was performed with fluorescently labeled antibodies to βIII-tubulin in wholemount corneal specimen on post-denervation day 7. Morphology of corneal endothelium and existence of inflammatory cells were evaluated on post- denervation day 7 using immunofluorescent staining. The proportion of apoptotic cells was assessed by TUNEL assay. Normal versus post-denervation corneal endothelium were collected on post- denervation day 7 for proteomic analysis.
Results :
Despite clear cornea with intact epithelium post-denervation, a substantail reduction in corneal sensation and nerve density was observed in the eye on post-denervation day 7 compared with a control eye. There was evidence of disruption in corneal endothelial cell junctions, an increased expression of TUNEL-positive cells, and CD45-positive cells. Comparative analysis of proteins on post-denervation day 7 revealed an up-regulation of proteins associated with the immune system, while proteins related to cytoskeleton and cell junction organization were largely down-regulated.
Conclusions :
Corneal endothelial cell loss and disrupted morphology were observed after denervation. The proteomic data imply that denervation induces an inflammatory response and dysregulation of cell junctions by the cytoskeleton. Our study's model suggests that denervation itself, without a secondary epithelial defect, can cause damage to the corneal endothelium.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.