title: Cellular and 3D optical coherence tomography assessment during the initiation and progression of retinal degeneration in the Ccl2/Cx3cr1-deficient mouse.
abstract: Retinal pathologies common to human eye diseases, including abnormal retinal pigment epithelial (RPE) cells, drusen-like accumulation, photoreceptor atrophy, and choroidal neovascularization, have been reported in the Ccl2/Cx3cr1-deficient mouse. The Ccl2 gene encodes the pro-inflammatory chemokine CCL2 (MCP-1), which is responsible for chemotactic recruitment of monocyte-derived macrophages to sites of inflammation. The Cx3cr1 gene encodes the fractalkine receptor, CX3CR1, and is required for accumulation of monocytes and microglia recruited via CCL2. Chemokine-mediated inflammation is implicated in retinal degenerative diseases such as diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, and uveoretinitis, and proper chemokine signaling from the RPE, Müller glia, and astrocytes is necessary to regulate leukocyte trafficking. Therefore, this mouse, possessing aberrant chemokine signaling coupled with retinal degenerative pathologies, presents an ideal opportunity to investigate the effect of altered signaling on retinal homeostasis and photoreceptor degeneration. Since this mouse is a recent development, more data covering the onset, location, and progression rate of pathologies is needed. In the present study we establish these parameters and show two photoreceptor cell death processes. Our observations of decreased glutamine synthetase and increased glial fibrillary acidic protein suggest that Müller cells respond very early within regions where lesions are forming. Finally, we suggest that retinal angiomatous proliferation contributes to pathological angiogenesis in this Ccl2/Cx3cr1-deficient mouse.
authors.affiliation: Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, School of Medicine, New Orleans, LA 70112, USA.
authors.forename: Yongdong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Kristopher G
authors.initials: KG
authors.lastname: Sheets
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Knott
authors.forename: Cornelius E
authors.initials: CE
authors.lastname: Regan
authors.forename: Jingsheng
authors.initials: J
authors.lastname: Tuo
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Chan
authors.forename: William C
authors.initials: WC
authors.lastname: Gordon
authors.forename: Nicolas G
authors.initials: NG
authors.lastname: Bazan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D000073883:CX3C Chemokine Receptor 1; D018932:Chemokine CCL2 / Q000502:physiology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005451:Fluorescein Angiography; D005904:Glial Fibrillary Acidic Protein; D005911:Gliosis / Q000378:metabolism / Q000473:pathology; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D021621:Imaging, Three-Dimensional; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009887:Ophthalmoscopy; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology*; D019707:Receptors, Chemokine / Q000502:physiology*; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology*; D041623:Tomography, Optical Coherence
chemical_list: D000073883:CX3C Chemokine Receptor 1; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C471885:Cx3cr1 protein, mouse; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D019707:Receptors, Chemokine; C528900:glial fibrillary astrocytic protein, mouse; D005974:Glutamate-Ammonia Ligase