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

Abstract

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-␤ 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

A Highly Efficacious Herpes Simplex Virus 1 Vaccine Blocks Viral Pathogenesis and Prevents Corneal Immunopathology via Humoral Immunity

“…Moreover, we also report preservation of corneal nerve sensitivity in challenged mice. This novel insight is relevant as neurogenic maintenance of immune privilege has also been suggested (67,68). Further substantiating the interplay of vaccine-mediated correlates of protection and prevention of ocular disease will also provide a basis for the development of vaccines or therapies for use against other ocular pathogens.…”

β2-Adrenoreceptor Agonist Inhibits Antigen Cross-Presentation by Dendritic Cells

“…The global effect of b-agonists on immunity was mainly studied by chemically depleting natural catecholamine stocks using 6-hydroxydopamine, which results in increased innate immune responses against bacteria (6), increased adaptive immune responses against virus (7), and decreased immune responses against Gram-positive bacteria (7)(8)(9). Additionally, surgical removal of the ocular sympathetic nerve affects the generation and maintenance of immune privilege in the eye (10). However, although these reports strongly suggest that the SNS regulates the magnitude and quality of immune responses via AR agonists, the molecular and cellular basis of this phenomenon remain unclear.…”

Impact of Type I Interferon on the Safety and Immunogenicity of an Experimental Live-Attenuated Herpes Simplex Virus 1 Vaccine in Mice

“…These include corneal scarring, neovascularization, and sensation loss, all of which are recapitulated in the animal model of ocular infection (11,45,46,51,70). Phylogenetic differences among virulence determinants in different HSV-1 strains are associated with various degrees of corneal neovascularization (71).…”