The analysis of systemic tolerance elicited by antigen inoculation into the vitreous cavity: vitreous cavity‐associated immune deviation

Abstract

SummaryThe immune privilege that exists in the eye is maintained by various mechanisms. One of the best studied is a form of systemic tolerance termed anterior chamber-associated immune deviation (ACAID). We have investigated the mechanisms by which ocular inflammation associated with the vitreous cavity (VC) is reduced, by injecting either ovalbumin (OVA) or allogeneic splenocytes into the VCs of mice, and assessed the effect of this on delayed type hypersensitivity (DTH) responses. After antigen inoculation into the VC, antigen-specific DTH responses were significantly impaired and we named this phenomenon 'vitreous cavityassociated immune deviation' (VCAID). VCAID could also be induced by inoculating antigen-pulsed macrophages into the VC. However, VCAID did not develop either in mice with inflamed eyes, whether as a result of experimental autoimmune uveitis or coadministration of interleukin (IL)-6 in the VC, or in knockout mice deficient for natural killer T (NKT) cells. Finally, we found that so-called 'hyalocytes' are the only cells present in the VCs of normal mice, uniformly distributed on the retinal surface. Interestingly, they express F4/80, suggesting that hyalocytes are candidate antigen-presenting cells (APCs) responsible for mediating VCAID. As for the anterior chamber model, systemic tolerance can be induced in the VC in non-inflamed eyes and in the presence of invariant NKT cells.

Can the Hair Follicle Become a Model for Studying Selected Aspects of Human Ocular Immune Privilege?

“…It is now known that the vitreous and subretinal space are also IP sites 107 and that antigens placed in these sites can even lead to the induction of an ACAID-like response. 22,54,55 In this context, it is interesting to note that (in mice) IP disruption occurs when RPE cells are damaged by laser burns. 18 This finding has raised the troubling question of whether laser-treated eyes are at increased risk of ocular inflammation, up to the collapse of eye IP.…”

Immune regulation and the eye

“…In other words, antigen injected into the anterior chamber [2], vitreous [3] or sub-retinal space [4] induces peripheral tolerance to that antigen. Furthermore, parts of the eye like the cornea are considered to be intrinsically immune privileged tissues because when transplanted to sites perfectly capable of rejecting foreign antigens, they enjoy acceptance.…”

Adult vitreous structure and postnatal changes

“…1 Recently, it has been suggested that they are involved in 'vitreous cavity-associated immune deviation'. 2 Despite our considerable knowledge of the composition and structure of the vitreous humour, its physiological functions remain unclear. There is evidence that it regulates eye growth and shape during development.…”