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Neal Mecum, Lei Lei, Ian D Meng; Sox11 Expression in the Trigeminal Ganglion Promotes Corneal Healing following Lacrimal Gland Excision. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):301.
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© ARVO (1962-2015); The Authors (2016-present)
Sox11, a transcription factor expressed in trigeminal and dorsal root ganglion neurons early in development, is induced in adult sensory neurons following nerve injury. As a promotor of nerve regeneration, we hypothesized that Sox11 may also be expressed during dry eye in order to increase trophic support to the cornea provided by corneal afferent neurons. The present study examined Sox11 expression and examined corneal epithelial integrity and mechanical sensitivity in Sox11 conditional knockout animals following lacrimal gland excision.
Male C57BL/6 mice were obtained from Jackson Labs and Sox11 conditional knockout (Sox11CKO) mice were generated using Cre-LoxP-mediated recombination under the control of a NaV1.8 promoter. Under isoflurane, unilateral lacrimal gland excision was performed. Either the left exorbital lacrimal gland, or both the exorbital and intraorbital lacrimal glands were excised. For sham surgeries, incisions were made and glands were partially exposed on the left side. Fluorescein solution was applied to the cornea in order to examine the corneal epithelial integrity. Corneal mechanical thresholds were determined using a Cochet-Bonnet esthesiometer. RNA from trigeminal tissue was isolated and samples were run using real time PCR.
In wild type animals, Sox11 expression in trigeminal ganglion increased 6-fold 3-days after lacrimal gland excision. Following both single and double gland excision, the severity of damage to the corneal epithelium was greater in Sox11 CKO animals when compared to excised controls. Furthermore, hypoesthesia of the cornea developed following lacrimal gland excision only in Sox11 CKO animals. No difference was observed between Sox11 CKO and control animals in corneal fluorescein staining or mechanical sensitivity after sham surgery.
These results indicate that dry eye induces Sox11 expression in the trigeminal ganglion, which maintains mechanical sensitivity and promotes healing of the corneal epithelium. Increasing Sox11 expression may prevent corneal damage caused by dry eye and other pathological conditions involving insufficient corneal innervation.
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