Immune cells in the retina and choroid: Two different tissue environments that require different defenses and surveillance

In the eye immune defenses must take place in a plethora of differing microenvironments ranging from the corneal and conjunctival epithelia facing the external environment to the pigmented connective tissue of the uveal tract containing smooth muscle, blood vessels and peripheral nerves to the innermost and highly protected neural retina. The extravascular environment of the neural retina, like the brain parenchyma, is stringently controlled to maintain conditions required for neural transmission. The unique physiological nature of the neural retina can be attributed to the blood retinal barriers (BRB) of the retinal vasculature and the retinal pigment epithelium, which both tightly regulate the transport of small molecules and restrict passage of cells and macromolecules from the circulation into the retina in a similar fashion to the blood brain barrier (BBB). The extracellular environment of the neural retina differs markedly from that of the highly vascular, loose connective tissue of the choroid, which lies outside the BRB. The choroid hosts a variety of immune cell types, including macrophages, dendritic cells (DCs) and mast cells. This is in marked contrast to the neural parenchyma of the retina, which is populated almost solely by microglia. This review will describe the current understanding of 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.