Sympathetic Corneal Nerves Mediate Contralateral Immune Responses in Unilateral Inflammation

Abstract

Purpose : Our group has recently demonstrated bilateral corneal immune cell alterations in clinically unilateral diseases. The purpose of the current study is to investigate the mechanism involved in this process and to study both ipsilateral and contralateral cornea immune responses after sensory and/or sympathetic nerve alterations.

Methods : Corneal thermal cautery, trigeminal nerve axotomy or cautery combined with ipsilateral or contralateral superior cervical ganglionectomy (sympathectomy; SCGx) were applied in this study. Both ipsilateral and contralateral corneas were excised on postoperative days (POD) 1, 3, 7 and 14 and immunofluorescence was performed on corneal whole-mounts with CD31, Lyve-1, and CD45. Analysis was performed with Imaris (Bitplane) to quantitatively assess the density of CD45⁺ cells in the limbus, peripheral and central cornea.

Results : Unilateral cautery resulted in increased CD45⁺ cell density in the limbus of both the ipsilateral (4999.6±128.7 cells/mm²) and contralateral (2480.6±252.7 cells/mm²) eyes at POD 1, compared to steady state (809.4±29.9 cells/mm², p<0.0001). Further, unilateral trigeminal axotomy resulted in increased limbal CD45⁺ cell density in the contralateral eyes as early as POD 1 (1316.3±133.8 cells/mm², p<0.001) continuing to POD 14 (1641.7±61.0 cells/mm², p<0.05). Cautery combined with SCGx in the same eye showed significantly decreased CD45⁺ cell density in both the ipsilateral (2878.6±171.2) and contralateral limbus (1534.1±93.4) compared to sham-treated cauterized eyes in all areas (p<0.0001). Finally, cautery in ipsilateral eyes and SCGx in contralateral eyes resulted in profound diminishment of the contralateral sympathetic immune response in all corneal areas (p<0.01) compared to contralateral eyes with intact sympathetic nerves.

Conclusions : Unilateral inflammation results in a contralateral immune response in unaffected eyes. When sympathectomy is performed in either eye, there is a significant diminishment in the contralateral immune response with complete abolishment of this sympathetic response with sympathectomy in the contralateral unaffected eyes. Our data suggests that the contralateral immune response is mediated by the sympathetic nervous system.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.