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Giulio Ferrari, Sunil K. Chauhan, Hiroki Ueno, Nambi Nallasamy, Stefano Gandolfi, Lawrence Borges, Reza Dana; A Novel Mouse Model for Neurotrophic Keratopathy: Trigeminal Nerve Stereotactic Electrolysis through the Brain. Invest. Ophthalmol. Vis. Sci. 2011;52(5):2532-2539. doi: 10.1167/iovs.10-5688.
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To develop a mouse model of neurotrophic keratopathy by approaching the trigeminal nerve through the brain and to evaluate changes in corneal cell apoptosis and proliferation.
Six- to 8-week-old male C57BL/6 mice underwent trigeminal stereotactic electrolysis (TSE) to destroy the ophthalmic branch of the trigeminal nerve. Clinical follow-up using biomicroscopy of the cornea was performed at days 2, 4, 5, and 7. To confirm the effectiveness of the procedure, we examined the gross nerve pathology, blink reflex, and immunohistochemistry of the corneal nerves. TUNEL-positive apoptotic and Ki-67–positive proliferating corneal cells were evaluated to detect changes from the contralateral normal eye.
TSE was confirmed by gross histology of the trigeminal nerve and was considered effective if the corneal blink reflex was completely abolished. TSE totally abolished the blink reflex in 70% of mice and significantly reduced it in the remaining 30%. Animals with absent blink reflex were used for subsequent experiments. In these mice, a progressive corneal degeneration developed, with thinning of the corneal epithelium and eventually perforation after 7 days. In all mice, 48 hours after TSE, corneal nerves were not recognizable histologically. Seven days after TSE, an increase in cellular apoptosis in all the corneal layers and a reduction in proliferation in basal epithelial cells were detected consistently in all mice.
TSE was able, in most cases, to induce a disease state that reflected clinical neurotrophic keratitis without damaging the periocular structures. Moreover, corneal denervation led to increased apoptosis and reduced proliferation of epithelial cells, formally implicating intact nerve function in regulating epithelial survival and turnover.
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