The retinal pigment epithelium as a gateway for monocyte trafficking into the eye

The choroid plexus epithelium within the brain ventricles orchestrates blood-derived monocyte entry to the central nervous system under injurious conditions, including when the primary injury site is remote from the brain. Here, we hypothesized that the retinal pigment epithelium (RPE) serves a parallel role, as a gateway for monocyte trafficking to the retina following direct or remote injury. We found elevated expression of genes encoding leukocyte trafficking determinants in mouse RPE as a consequence of retinal glutamate intoxication or optic nerve crush (ONC). Blocking VCAM-1 after ONC interfered with monocyte infiltration into the retina and resulted in a local pro-inflammatory cytokine bias. Live imaging of the injured eye showed monocyte accumulation first in the RPE, and subsequently in the retina, and peripheral leukocytes formed close contact with the RPE. Our findings further implied that the ocular milieu can confer monocytes a phenotype advantageous for neuroprotection. These results suggest that the eye utilizes a mechanism of crosstalk with the immune system similar to that of the brain, whereby epithelial barriers serve as gateways for leukocyte entry. Synopsis The retinal pigment epithelium (RPE) acts as the primary entry point for infiltrating monocytes during retinal injury to positively contribute to the restoration of immunological balance in the retinal milieu. A video of this synopsis is available online at http://embopress.org/video-EMBOJ-2016-94202 The epithelial barriers of the central nervous system display immunomodulatory capacity. The expression of leukocyte trafficking determinants is elevated in the retinal pigment epithelium (RPE) of the eye upon direct or remote injury to retinal ganglion cells. Live imaging of the injured eye demonstrates the sequential accumulation of monocytes, first in the RPE and then in the retina. The ocular milieu can confer monocytes a phenotype that is advantageous for restoration of immunological balance and for neuroprotection. The retinal pigment epithelium acts as the primary entry point for infiltrating monocytes during retinal injury to positively contribute to the restoration of immunological balance in the retinal milieu.