Are There Apcs In The Retina

While the concept of the blood-retinal barrier (and blood-brain barrier) has been fashioned on the basis of limiting passage of large molecules from the blood stream into the neural parenchymal tissue (79) it was believed for many years that these barriers naturally extend to blood-borne cells. However, inflammatory processes do occur in the brain and retina and there is evidence that the normal central nervous system (CNS) is subject to regular "patrol" by lymphocytes, most likely of the activated or blast form since resting T cells do not normally enter the CNS parenchyma (80). This is supported by evidence that in autoimmune conditions, such as multiple sclerosis or uveitis, autoreactive T cells do indeed enter the CNS or eye, respectively. A paradigm has emerged that low numbers of lymphocytes, albeit activated, access and "patrol" the CNS parenchyma for potential pathogens (81). If, as evidence to date would indicate, DCs are excluded from the normal neural retina (and brain parenchyma), which cell type within the neural retina acts to present Ag to patrolling activated T cells? If, as outlined earlier, it is accepted that DCs act as the sentinels in the afferent arm of immune responses by sampling Ag in peripheral tissue and regularly migrate to draining lymphoid tissues, one must therefore conclude that this sort of immune surveillance does not occur within the CNS parenchyma and neural retina.

The evolutionary and developmental basis of immune responses within the CNS has recently been reviewed (82). It is convincingly argued that the lack of DCs in the CNS parenchyma (including neural retina) is due to the late evolution of both the adaptive immune system and meninges. The meninges in mammals contain rich populations of macrophages and DCs (83). While primitive meninges are present in cartilaginous fish, the three distinct layers (pia mater, arachnoid, and dura mater) as seen in mammals become identifiable in amphibians and appear to have co-evolved alongside the adaptive immune system. As further support for this co-evolutionary argument, Lowenstein (82) points out that the meninges appear in fetal development around the same time as key elements of the adaptive immune system. It is appealing to consider that similar arguments could be made for the neural retina.

Candidate APCs in the retina include firstly parenchymal cells such as astrocytes, oligodendrocytes, and endothelium and secondly non-parenchymal haematogenous-derived immune cells including microglia (MG) and perivascular macrophages. The potential role of parenchymal cells as APCs in the context of the CNS has been reviewed elsewhere (84). The following discussion will focus on retinal MG and perivascular as these are considered the most likely APCs.

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