The privileged immunity of immune privileged organs: the case of the eye

Abstract

Understanding of ocular diseases and the search for their cure have been based on the common assumption that the eye is an immune privileged site, and the consequent conclusion that entry of immune cells to this organ is forbidden. Accordingly, it was assumed that when immune cell entry does occur, this reflects an undesired outcome of breached barriers. However, studies spanning more than a decade have demonstrated that acute insults to the retina, or chronic conditions resulting in retinal ganglion cell loss, such as in glaucoma, result in an inferior outcome in immunocompromised mice; likewise, steroidal treatment was found to be detrimental under these conditions. Moreover, even conditions that are associated with inflammation, such as age-related macular degeneration, are not currently believed to require immune suppression for treatment, but rather, are thought to benefit from immune modulation. Here, we propose that the immune privilege of the eye is its ability to enable, upon need, the entry of selected immune cells for its repair and healing, rather than to altogether prevent immune cell entry. The implications for acute and chronic degenerative diseases, as well as for infection and inflammatory diseases, are discussed.

Keywords: immune privilege; immunomodulation; inflammation; neuroprotection and neuronal repair; visual system.

FIGURE 1

An evolving view of immune involvement in the eye. Ocular pathologies are initiated by multiple factors, and take on various manifestations. Glaucoma, a slowly progressing neurodegenerative disease, is characterized by loss of retinal ganglion cells and damage to the optic nerve. In posterior uveitis, retinal atrophy, and neuronal death are commonly induced by autoimmune inflammation, and age-related macular degeneration presents with drusen (“dry” AMD) and choroidal neovascularization (“wet” AMD). While the traditional dogma stated that immune privilege implies the exclusion of immune activity from the eye under any circumstances, our evolving understanding of immune privilege proposes that boosting beneficial immunity in the eye, in a well-regulated manner, rather than general immune suppression, is most favorable for coping with ocular pathologies, regardless of their initiating factors.