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Gerhild Wildner, Maria Diedrichs-Möhring, Stephan R Thurau; New treatment options for chorioretinal neovascularizations mediated by autoreactive T cells in rat EAU. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2536.
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© ARVO (1962-2015); The Authors (2016-present)
Neovascularization in the retina as a consequence of inflammation is a major problem in the eye. We have recently shown that VEGF-producing autoreactive T cells in rat experimental autoimmune uveitis can also induce chorioretinal neovascularization (CNV). Here we investigate the expression of CD146, a molecule of endothelial tight junctions and a coreceptor of VEGFR-2, in the eye and the effect of antibody to CD146 on EAU and formation of CNV.
To induce clinically monophasic uveitis with neovascularizations Lewis rats were immunized with S-Ag peptide PDSAg-CFA or adoptively transferred with PDSAg-specific T cells. After adoptive transfer anti-CD146 antibody was daily injected s.c. and uveitis intensity monitored clinically and histologically. To investigate the effect on CNV formation, anti-CD146 antibody was injected once into the anterior chamber of rats one day prior to onset of clinical disease and CNV formation determined histologically. Cryosections from rat eyes with EAU were stained with anti-CD31/PECAM and anti-CD146.
In eyes with EAU CD146 was expressed in the choroid/choriocapillaris and CNV, also on some infiltrating T cells. Preventive systemic or intraocular treatment with anti-CD146 only marginally affected the intensity of intraocular inflammation, while a single intraocular injection of anti-CD146 prior disease onset significantly suppressed CNV formation.
Anti-CD146 antibodies can prevent the pathological development of new vessels in the eye after a single intraocular injection in an EAU model, where autoreactive T cells produce VEGF and induce CNV. Targeting this molecule could be a new therapeutic option to prevent the growth of new blood vessels.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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