title: Role of fractalkine/CX3CR1 interaction in light-induced photoreceptor degeneration through regulating retinal microglial activation and migration.
abstract: BACKGROUND
  Excessive exposure to light enhances the progression and severity of some human retinal degenerative diseases. While retinal microglia are likely to be important in neuron damage associated with these diseases, the relationship between photoreceptor damage and microglial activation remains poorly understood. Some recent studies have indicated that the chemokine fractalkine is involved in the pathogenesis of many neurodegenerative diseases. The present study was performed to investigate the cross-talk between injured photoreceptors and activated retinal microglia, focusing on the role of fractalkine and its receptor CX3CR1 in light-induced photoreceptor degeneration.
  
  
  RESULTS
  Both in vivo and in vitro experiments were involved in the research. In vivo, Sprague-Dawley rats were exposed to blue light for 24 hours. In vitro, the co-culture of primary retinal microglia and a photoreceptor cell line (661W cell) was exposed to blue light for five hours. Some cultures were pretreated by the addition of anti-CX3CR1 neutralizing antibody or recombinant fractalkine. Expression of fractalkine/CX3CR1 and inflammatory cytokines was detected by immunofluorescence, real-time PCR, Western immunoblot analysis, and ELISA assay. TUNEL method was used to detect cell apoptosis. In addition, chemotaxis assay was performed to evaluate the impact of soluble fractalkine on microglial migration. Our results showed that the expression of fractalkine that was significantly upregulated after exposure to light, located mainly at the photoreceptors. The extent of photoreceptor degeneration and microglial migration paralleled the increased level of fractalkine/CX3CR1. Compared with the control, the expression of inflammatory cytokines was significantly downregulated in the anti-CX3CR1 neutralizing antibody-treated group, and the number of photoreceptors was also well preserved. The addition of recombinant full-length fractalkine or soluble fractalkine resulted in fewer TUNEL-positive photoreceptors and an increased number of migratory microglia respectively.
  
  
  CONCLUSIONS
  These findings demonstrate that fractalkine/CX3CR1 interaction may play an important role in the photoreceptor-microglia cross-talk in light-induced photoreceptor degeneration.
authors.affiliation: Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, People's Republic of China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.forename: Gezhi
authors.initials: G
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Yingqin
authors.initials: Y
authors.lastname: Ni
authors.forename: Wenting
authors.initials: W
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D000073883:CX3C Chemokine Receptor 1; D002465:Cell Movement; D048430:Cell Shape; D002478:Cells, Cultured; D054428:Chemokine CX3CL1 / Q000378:metabolism / Q000502:physiology*; D018920:Coculture Techniques; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008027:Light / Q000009:adverse effects*; D017628:Microglia / Q000378:metabolism / Q000502:physiology*; D010786:Photoreceptor Cells / Q000378:metabolism / Q000528:radiation effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019707:Receptors, Chemokine / Q000378:metabolism*; D012160:Retina / Q000473:pathology / Q000528:radiation effects; D012162:Retinal Degeneration / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000073883:CX3C Chemokine Receptor 1; C516305:CX3CR1 protein, rat; D054428:Chemokine CX3CL1; C515540:Cx3cl1 protein, rat; D053583:Interleukin-1beta; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha