Role of the chemokine receptor CX3CR1 in the mobilization of phagocytic retinal microglial cells.
We recently showed that subretinal CX3CR1-dependent microglial cell (MC) accumulation may lead to age-related macular degeneration. The fate of MC after engulfing retinal debris is poorly understood. Severe photoreceptor degeneration was observed 40days after exposure to bright light in CX3CR1-deficient but not control mice, and more MCs accumulated in the subretinal space of the former than the latter. To study the fate of subretinal MCs in CX3CR1 competent animals, we used a dystrophic rat model in which abundant subretinal MC accumulation is observed secondary to retinal degeneration. In dystrophic rats, MCs containing rhodopsin or rod outer segment (ROS) debris were found outside the outer retina at sites suggesting choroidal and ciliary egress. In conclusion, our data indicate that MC accumulation at injury sites is independent of CX3CR1 and precedes photoreceptor degeneration. The ectopic presence of rhodopsin-positive MCs suggests that CX3CR1 participates in MC egress from the outer retina.
Raoul
William
W
INSERM, UMR S 872, Centre de Recherche des Cordeliers, F-75006, Paris, France. william.raoul@crc.jussieu.fr
Keller
Nicole
N
Rodéro
Mathieu
M
Behar-Cohen
Francine
F
Sennlaub
Florian
F
Combadière
Christophe
C
D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D002465:Cell Movement / Q000502:physiology; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008027:Light / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000502:physiology* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission / Q000379:methods; D010586:Phagocytes / Q000502:physiology* / Q000648:ultrastructure; D010587:Phagocytosis / Q000235:genetics; D010786:Photoreceptor Cells / Q000378:metabolism / Q000648:ultrastructure; D019707:Receptors, Chemokine / Q000172:deficiency / Q000502:physiology*; D012160:Retina / Q000166:cytology*; D012162:Retinal Degeneration / Q000209:etiology / Q000473:pathology*; D012243:Rhodopsin / Q000378:metabolism; D018709:Statistics, Nonparametric; D013997:Time Factors
D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D019707:Receptors, Chemokine; D049452:Green Fluorescent Proteins; D012243:Rhodopsin