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.
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
Inbal
I
Benhar
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
Kitty
K
Reemst
Department of Veterinary Resources, Weizmann Institute of Science, Rehovot, Israel.
Vyacheslav
V
Kalchenko
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel michal.schwartz@weizmann.ac.il.
Michal
M
Schwartz
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology; D000073883:CX3C Chemokine Receptor 1; D002634:Chemotaxis, Leukocyte; D015870:Gene Expression; D018698:Glutamic Acid / Q000633:toxicity; D049452:Green Fluorescent Proteins / Q000235:genetics; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology*; D020221:Optic Nerve Injuries / Q000276:immunology; D018121:Receptors, Cytokine / Q000235:genetics; D015728:Receptors, HIV / Q000235:genetics; D055213:Retinal Pigment Epithelium / Q000276:immunology*; D012173:Retinitis / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology
D000073883:CX3C Chemokine Receptor 1; D018121:Receptors, Cytokine; D015728:Receptors, HIV; D019010:Vascular Cell Adhesion Molecule-1; D049452:Green Fluorescent Proteins; D018698:Glutamic Acid
monocyte‐derived macrophages; neuroprotection; optic nerve crush; retinal ganglion cells; retinal pigment epithelium