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Carl F Marfurt, Jaclyn O'Connell, Aliya Khan; Innervation of the murine cornea. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):296.
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© ARVO (1962-2015); The Authors (2016-present)
The mouse corneal innervation is a popular model for studies of dry eye disease, ocular pain mechanisms, and corneal nerve regeneration; however, detailed descriptions of the healthy mouse corneal innervation are sparse. The purpose of the current investigation is to describe in detail the morphology of the normal murine corneal innervation.
Forty eight corneas from 2-3 month-old BALB/c mice were enucleated, immersion-fixed in 4% paraformaldehyde, and permeabilized with either 2% Triton-X 100 or hyaluronidase/EDTA. Nerves were visualized in corneal whole mounts by immunohistochemical staining with a primary antiserum against neurotubulin (Covance). Ciliary nerves, stromal bundles, subbasal nerve fibers (SNFs) and intraepithelial terminals were subjected to rigorous quantitative and qualitative analyses.
A total of 4-6 ciliary nerves per eye (X=4.94+/-0.62) entered the posterior globe in proximity to the optic nerve and radiated, with minimal additional branching, towards the anterior segment. At the corneoscleral limbus, the ciliary nerves branched and gave origin to 29.63+/-2.83 radially-oriented main stromal nerve bundles per cornea. The stromal nerves branched and anastomosed extensively to form a modest subepithelial nerve plexus which in turn gave origin to a dense subbasal nerve plexus. SNFs radiated in curvilinear fashion towards the corneal apex where they converged in a periapical location via one of four main patterns: a clockwise spiral (62.1% of cases), counter-clockwise spiral (35.6%), radially symmetrical convergence (6.67%) or mixed (linear seam plus a spiral, 6.67%). The center of SNF convergence was located most frequently slightly inferonasal to the corneal apex. Intraepithelial nerve terminal density averaged 908 terminals/mm2 in the 1mm-diameter area centered on the corneal apex, then decreased progressively to 658/mm2 in the intermediate cornea, 429/mm2 in the peripheral cornea, and 220/mm2 in the perilimbus. Nerve terminal density was especially high (2324/mm2) in a 0.2mm-diameter zone of epithelium centered over the SNF vortex.
The results of this study provide a detailed quantitative and qualitative description of the normal mouse corneal innervation. The data should provide a useful baseline reference for future studies of altered corneal innervation density and morphology in ocular diseases or after corneal nerve injury.
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