| First Author | Aredo B | Year | 2015 |
| Journal | J Neuroinflammation | Volume | 12 |
| Pages | 6 | PubMed ID | 25588310 |
| Mgi Jnum | J:280607 | Mgi Id | MGI:6367874 |
| Doi | 10.1186/s12974-014-0221-4 | Citation | Aredo B, et al. (2015) Differences in the distribution, phenotype and gene expression of subretinal microglia/macrophages in C57BL/6N (Crb1 rd8/rd8) versus C57BL6/J (Crb1 wt/wt) mice. J Neuroinflammation 12:6 |
| abstractText | BACKGROUND: Microglia/macrophages (MG/MPhi) are found in the subretinal space in both mice and humans. Our goal was to study the spatial and temporal distribution, the phenotype, and gene expression of subretinal MG/MPhi in mice with normal retinas and compare them to mice with known retinal pathology. METHODS: We studied C57BL/6 mice with (C57BL/6N), or without (C57BL/6J) the rd8 mutation in the Crb1 gene (which, in the presence of yet unidentified permissive/modifying genes, leads to a retinal degeneration), and documented their fundus appearance and the change with aging. Immunostaining of retinal pigment epithelium (RPE) flat mounts was done for 1) Ionized calcium binding adaptor (Iba)-1, 2) FcgammaIII/II Receptor (CD16/CD32, abbreviated as CD16), and 3) Macrophage mannose receptor (MMR). Reverse-transcription quantitative PCR (RT-qPCR) was done for genes involved in oxidative stress, complement activation and inflammation. RESULTS: The number of yellow fundus spots correlated highly with subretinal Iba-1+ cells. The total number of subretinal MG/MPhi increased with age in the rd8 mutant mice, but not in the wild-type (WT) mice. There was a centripetal shift in the distribution of the subretinal MG/MPhi with age. Old rd8 mutant mice had a greater number of CD16+ MG/MPhi. CD16+ cells had morphological signs of activation, and this was most prominent in old rd8 mutant mice (P < 1 x 10(-8) versus old WT mice). Subretinal MG/MPhi in rd8 mutant mice also expressed iNOS and MHC-II, and had ultrastructural signs of activation. Finally, rd8 mutant mouse RPE/ MG/MPhi RNA isolates showed an upregulation of Ccl2, CFB, C3, NF-kbeta, CD200R and TNF-alpha. The retinas of rd8 mutant mice showed upregulation of HO-1, C1q, C4, and Nrf-2. CONCLUSIONS: When compared to C57BL/6J mice, C57BL/6N mice demonstrate increased accumulation of subretinal MG/MPhi, displaying phenotypical, morphological, and gene-expression characteristics consistent with a pro-inflammatory shift. These changes become more prominent with aging and are likely due to the combination of the rd8 mutation and yet unidentified permissive/modulatory genes in the C57BL/6N mice. In contrast, aging leads to a scavenging phenotype in the C57BL/6J subretinal microglia/macrophages. |
