Elegant work by Bruttger et al. the distribution, phenotype and physiological role of ocular immune cells behind or inside the blood-retinal barriers and those in closely juxtaposed tissues outside the barrier. The nature and function of these immune cells can profoundly influence retinal homeostasis and lead to disordered immune function that can lead to vision loss. (Forrester et al., 2016). The choroid contrasts sharply in structure and function to the neural retina. It is a highly vascularised, pigmented loose connective tissue that constitutes the posterior part of the uveal tract (Fig. 1ACC). It supplies trophic and metabolic support to the outer retina. It is homologous to the pia-arachnoid of the brain and its vessels do not feature the stringent barrier properties of those within the retina or brain parenchyma; indeed, the capillary bed of the choroid, the choriocapillaris, is highly fenestrated (Fig. 1D and ?andE).E). The choroid lies internal to the sclera, which consists of dense irregular connective tissue, the homologue of the dura mater with which it is continuous at Rabbit Polyclonal to TRXR2 the optic nerve. Just as advances in the field of meningeal immunity have begun to reveal the complex nature of this compartment and its role in directing and coordination of immune cell traffic throughout the CNS (Rua and McGavern, 2018), it is likely that we are at the Promazine hydrochloride beginning of a similar renaissance in awareness of the importance of the immune system in the choroid to retinal health. Like other loose connective tissues, including the leptomeninges Promazine hydrochloride (Chinnery et al., 2010; Coles et al., 2017; McMenamin, 1999b; Rua and McGavern, 2018), the normal mammalian choroid contains networks of tissue macrophages, dendritic cells (DCs) and mast cells (Chinnery et al., 2017; Forrester et al., 2010; McMenamin, 1997, 1999a). The recent re-discovery of lymphatics in the dura of the mouse brain (Aspelund et al., 2015; Louveau et al., 2015, 2016) has heightened the search for uveal tract lymphatics in mammals; however, to date there is no convincing evidence of choroidal lymphatics in the mammalian eye (Schroedl et al., 2014). A more detailed discussion on the role of so-called glymphatics in drainage of interstitial fluid in the brain parenchyma and its potential role as a route for immune cell trafficking is discussed in detail elsewhere Promazine hydrochloride (Forrester et al., 2018b). Within the closely related and anatomically approximated ocular microenvironments of the neural retina and choroid exists a contrast in the nature of immune cells that are essential to immune surveillance and defense, ranging from the highly specialized MG population of the retina to the diverse array of macrophages, DCs and mast cells of the choroid. These two highly specialized defense systems must both support homeostatic functions and yet coordinate appropriate inflammatory responses to pathogenic or injurious stimuli. Whilst there may be a degree of so-called immune privilege in the retina the occurrence of a range of diseases such as uveoretinitis, retinal vasculitis in Bechets disease and various pathogen driven inflammatory diseases reminds us that this protected environment can indeed be the site of vision threatening inflammatory or immune-mediated disease. Similarly, the choroid is not exempt from immune-mediated disease with autoimmune responses to melanocyte-specific antigens being.