Redefining our vision: an updated guide to the ocular immune system

Balanced immune responses in the eyes are crucial to preserve vision. The ocular immune system has long been considered distinct, owing to the so-called ‘immune privilege’ of its component tissues. More recently, intravital imaging and transcriptomic techniques have reshaped scientific understanding of the ocular immune landscape, such as revealing the specialization of immune cell populations in the various tissues of the eye. As knowledge of the phenotypes of corneal and retinal immune cells has evolved, links to both the systemic immune system, and the central and peripheral nervous systems, have been identified. Using intravital imaging, T cells have recently been found to reside in, and actively patrol, the healthy human cornea. Disease-associated retinal microglia with links to retinal degeneration have also been identified. This Review provides an updated guide to the ocular immune system, highlighting current knowledge of the immune cells that are present in steady-state and specific diseased ocular tissues, as well as evidence for their relationship to systemic disease. In addition, we discuss emerging intravital imaging techniques that can be used to visualize immune cell morphology and dynamics in living human eyes and how these could be applied to advance understanding of the human immune system. This Review provides an overview of the immune system of the eye at steady state and in ocular disease, and it describes the links between ocular immunology and systemic disease. It highlights the intravital imaging techniques that have provided insights into immune cell morphology and dynamics in living human eyes.