The expression of ICOSL in the cornea and the ICOS-mediated induction of Foxp3+ CD4+ regulatory T cells may contribute to successful corneal allograft survival.
Citation: Kunishige T, Taniguchi H, Ohno T, Azuma M, Hori J. VISTA is crucial for corneal allograft survival and maintenance of immune privilege. Invest Ophthalmol Vis Sci. 2019;60:4958-4965. https://doi.org/ 10.1167/iovs.19-27322 PURPOSE. V-domain immunoglobulin suppressor of T cell activation (VISTA) is a novel immune checkpoint receptor and ligand for regulating T cell proliferation and cytokine production. The purpose of the present study was to determine the role of VISTA in the immune privilege of corneal allografts.METHODS. Expression of VISTA mRNA in mouse eyes was assessed with reverse-transcription PCR. Corneas of C57BL/6 mice were orthotopically transplanted into the eyes of BALB/c wildtype recipients treated with anti-VISTA mAb, and graft survival was assessed. A separate set of BALB/c mice treated with anti-VISTA mAb or rat IgG received injection of C57BL/6 splenocytes into the anterior chamber, and induction of allospecific anterior chamberassociated immune deviation (ACAID) was assessed. CD4 þ and CD8 þ T cells in the spleen were assessed with flow cytometry.
RESULTS.VISTA mRNA was constitutively expressed in the cornea, and the expression of VISTA was localized to CD11b þ cells on the corneal stroma. Survival of allografts treated with anti-VISTA mAb was less than that of the control. ACAID was induced less efficiently in BALB/c mice treated with VISTA mAb. The proportions of CD8 þ T cells and CD8 þ CD103 þ T cells (CD8 þ T regulatory cells) in the spleen of BALB/c mice treated with anti-VISTA mAb were significantly lower than those of the control.CONCLUSIONS. VISTA may play an essential role in the acceptance of corneal allografts via involvement with allospecific ACAID, which suppresses T cell infiltration into the cornea.
The eye is provided with immune protection against pathogens in a manner that greatly reduces the threat of inflammation-induced vision loss. Immune-mediated inflammation and allograft rejection are greatly reduced in the eye, a phenomenon called ‘immune privilege’. Corneal tissue has inherent immune privilege properties with underlying three mechanisms: (1) anatomical, cellular, and molecular barriers in the cornea; (2) an immunosuppressive microenvironment; and (3) tolerance related to regulatory T cells and anterior chamber-associated immune deviation. This review describes the molecular mechanisms of the immunosuppressive microenvironment and regulatory T cells in the cornea that have been elucidated from animal models of ocular inflammation, especially those involving corneal transplantation, it also provides an update on immune checkpoint molecules in corneal and systemic immune regulation, and its relevance for dry eye associated with checkpoint inhibitor therapy.
We examined the effects of different ophthalmic viscosurgical devices (OVDs) and suction flow rates during phacoemulsification on the amount of ultrasound power used and damage to the corneal endothelium. In total, 48 eyes of 24 patients who underwent phacoemulsification and intraocular lens insertion with different OVD settings in the left and right eye between February and August 2018 were examined retrospectively from medical records. Each of the following types of OVDs was used in either the right or left eye of each patient: a viscoadaptive OVD (V group) or a combination of dispersive and cohesive OVDs (soft-shell technique; S group). There was no significant difference in the lens nucleus hardness between the two groups. A 2.4 mm transconjunctival scleral incision was made, and phacoemulsification was performed by the same surgeon. The cumulative dissipated energy (CDE) and ultrasound time intraoperatively were compared between the two groups. The CDE was significantly larger in the V group (9.9 ± 4.6) than the S group (6.4 ± 3.0; p=0.006). The reduction rate of the endothelial cell density at the center of the cornea was significantly higher in the V group (4.1% ± 6.7%) than the S group (0.3% ± 4.5%; p=0.03) at 1 week postoperatively. Both groups had a good postoperative course. There was less corneal endothelial damage with the soft-shell technique combined with a normal flow setting than the viscoadaptive OVD combined with a low flow setting.
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