Surgical Denervation of Ocular Sympathetic Afferents Decreases Local Transforming Growth Factor-beta and Abolishes Immune Privilege

Mounting evidence points to a role for the sympathetic nervous system in suppressing inflammation. This role might be of specific relevance for immune privilege in the eye, where, sporadically, patients with denervated sympathetic fibers develop chronic inflammation. The present study used mice to investigate whether the robust innervation of intraocular structures by the sympathetic system plays a role in maintaining ocular immune privilege. We first performed surgical removal of the superior cervical ganglion, which supplies sympathetic fibers to the eye, and studied the immune response generated against soluble antigens or allogeneic tumor cells injected into the ocular anterior chamber under these conditions. Our results show that in the absence of functional sympathetic fibers, the eye loses its ability to prevent either the immune rejection of intraocular allogeneic tumor cells or the suppression of delayed type hypersensitivity responses against soluble antigens injected in the anterior chamber. This loss of immune privilege is accompanied by a decrease in the concentration of transforming growth factor-beta in the aqueous humor. These results suggest that immune privilege is lost in the absence of a functional sympathetic innervation of the eye, allowing intraocular immune responses to become exaggerated. We conclude that ocular sympathetic nerves are critical for the generation and maintenance of immune privilege in the eye through the facilitation of local transforming growth factor-beta production. (Am J Pathol 2009, 175:1218-1225; DOI: 10.2353/ajpath.2009.090264)