Abstract
Purpose :
To examine the phenotype of cornea in a mouse with severe damage in ophthalmic V1 branch of trigeminal nerve. We previously reported that partial damage with a thinner (20-guage) needle in V1 nerve attenuates stemness of limbal basal cells and impairs healing of central corneal debridement in mice (Okada et al, Lab Invest 2019). While the phenotype of cornea with severe V1 nerve damage by an 18-guage needle is to be investigated so far in mice.
Methods :
V1 nerve was severely coagulated by inserting an 18-gauge bipolar needle through the skull in C57Bl/6 mice as we previously reported (Okada et al, Lab Invest 2019). Mice were sacrificed at the time-points from 1 day to 24 months. Cornea was processed for histology and immunohistochemistry for alpha smooth muscle actin, F4/80 macrophage marker, keratinization marker (Filaggrin), intercellular adhesion marker (Connexin43), stem cell markers (ABCG2, Hes1) and Keratin 1, 12, 14 as a detector of cornea-type epithelial differentiation.
Results :
Corneal opacity with inflammation in the stroma and ulceration spontaneously developed in 1 day after severe V1 nerve damage. Histology showed both epithelium and stroma were severely damaged during earlier periods up to 3 months. Myofibroblasts and macrophages were observed in the stroma up to 3 months. Expression of ABCG2 and Hes1 was markedly attenuated in limbus. In the cornea at 14 and 24 months of time-points, the stroma was found to be much thinner with a keratinized epithelial hyperplasia. Markers of keratinization keratin 1 and Connexin 43 are not expressed in uninjured corneal epithelium, but are expressed in the corneal epithelium after 1 year. Such epithelium no longer express keratin 12 and 14.
Conclusions :
Neurotrophic keratopathy with severe V1 nerve damage causes spontaneous inflammation and loss of stem cells in cornea. Such phenotype was followed by the loss of cornea-type differentiation in epithelium associated with keratinization and stromal decomposition.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.