Depletion of NKi Cells Suppresses Laser-Induced Choroidal Neovascularization (NV), but not Ischemia-Induced Retinal NV or NV Due to Overexpression of VEGF

Abstract

Purpose: Invariant natural killer T cells (iNKT) cells are a subpopulation of T cells that exhibit both innate and adaptive immune function. These cells express an invariant receptor (Vα24, Jα18, Vβ11 in humans) that is similar in all individuals and responds to CD1d presented endogenous and expogenous glycolipids with the release of both type 1 and type 2 cytokines and inflammatory mediators. Recent evidence suggests a possible role for iNKT cells in retinal neovascularization (NV). In this study, we examined the effect of iNKT cell depletion on choroidal, subretinal, and retinal NV using an antibody (NKT14) that recognizes the iTCR of mouse iNKT cells and specifically depletes Murine iNKT cells via the antibody-dependent cell-mediated cytotoxicity(ADCC).

Methods: NKT14 A was dosed by subcutaneous injection at a dose of 50ug that was previously demonstrated to deplete iNKT cells. NKT 14 was dosed prior to laser-induced rupture of Bruch’s membrane, prior to the ischemic period in mice with oxygen-induced ischemic retinopathy, in rho/VEGF transgenic mice, or in very-low density lipoprotein receptor (VLDLR) mutant mice. Retinas or choroids were stained with GSA lectin and the area of NV was compared in flat mounts from iNKT cell-depleted and control mice.

Results: Depletion of iNKT cells suppressed choroidal NV.The mean area of CNV was 0.005 ±0.0005/mm² in the NKT14 treated group (n=19) and 0.008±0.001 /mm² in the isotype IgG injected control group (n=20) (P=0.001). However it had no effect on retinal NV in mice with ischemic retinopathy, the extent of subretinal NV in rho/VEGF transgenics, or the subretinal NV in VLDLR mutant mice.

Conclusions: lNKT cells appear to be a factor in the development of choroidal NV, However depletion of iNKT cells did not modulate ischemia-induced retinal NV or spontaneous subretinal NV in rho/VEGF mice or VLDLR mutant mice. . Additional studies are needed to determine why the participation of lNKT cells differs in these different types of ocular NV.