Immune privilege persists in eyes with extreme inflammation induced by intravitreal LPS

Abstract

Since immune privilege is believed to exist in the eye in order to suppress sight‐destroying inflammation, we wondered whether eyes with intraocular inflammation retain the immune privileged state. Intraocular inflammation was induced by injection of lipopolysaccharide (LPS) into the vitreous cavity of BALB / c mouse eyes, which showed a peak in intensity at approximately 9 h. At this time point, inflamed eyes were examined for their capacity to afford immune privilege to injected allogeneic tumor cells, and to promote anterior chamber‐associated immune deviation (ACAID) to antigens injected locally. In addition, aqueous humor (AqH) harvested from inflamed eyes was tested for its ability to suppress T cell activation. Surprisingly, eyes with acute, intense intraocular inflammation allowed allogeneic tumor cells to form progressively growing tumors, and these same eyes promoted ACAID. Moreover, AqH harvested from inflamed eyes strongly inhibited T cell activation. We conclude that the type of extreme, intraocular inflammation evoked by intravitreally injected LPS fails to abolish immune privilege in the eye. These findings are discussed in light of the effects of other types of inflammation on the integrity of ocular immune privilege, and with respect to the capacity of the eye to maintain immune privilege by more than one mechanism.

Impact of Inflammation on Ocular Immune Privilege

“…The presence of ACAID was not tested in these animals because the large amount of LPS received by these mice prevented the development of delayed-type hypersensitivity (DTH). EIU was also induced by intravitreal injection of a tiny amount (1 ng) of LPS (local EIU) [4]. In order to produce an intense intraocular inflammation in BALB/c mice without influencing the systemic immune system, one ng of LPS was injected into the vitreous cavity of the BALB/c mouse.…”

“…T cells) [3]. The ocular immunosuppressive microenvironment can be analyzed in vitro by studying the capacity of AH to suppress T cell proliferation stimulated by anti-CD3 monoclonal antibody (2C11) [4]. Small neuropeptides and latent transforming growth factor (TGF)-␤ are present in native AH.…”

Total protein concentration and T-cell suppression activity of aqueous humour before and after penetrating keratoplasty

“…26 Similarly, AqH from the eyes of mice in which anterior uveitis has been induced with an intravitreal injection of bacterial lipopolysaccharide is profoundly inhibitory of T-cell activation in vitro. 21 The immunosuppressive factor closely linked with suppression in these uveitic eyes is active TGF-b. This is in line with previous reports that suggest that high levels of TGF-b may be protective for immune reactions after PK.…”

“…21 Spleens were removed from naive BALB/c mice and pressed through nylon mesh to produce single-cell suspensions. Red blood cells were lysed with Tri-NH 4 Cl.…”

Estudo da toxicidade do adalimumabe (Humira®) intravítreo para a retina de coelhos

“…Os agentes formulados para outras vias de administração podem conter formulações subótimas do composto terapêutico, pH impróprio ou podem conter níveis inaceitáveis de contaminantes, como a endotoxina. A endotoxina é um componente da parede celular das bactérias que está comumente presente durante o processo de manufatura farmacêutica, e pode causar reação inflamatória grave quando injetada no vítreo (196) .…”