| First Author | Badia A | Year | 2021 |
| Journal | Exp Eye Res | Volume | 203 |
| Pages | 108424 | PubMed ID | 33373623 |
| Mgi Jnum | J:305491 | Mgi Id | MGI:6705820 |
| Doi | 10.1016/j.exer.2020.108424 | Citation | Badia A, et al. (2021) Transcriptomics analysis of Ccl2/Cx3cr1/Crb1(rd8) deficient mice provides new insights into the pathophysiology of progressive retinal degeneration. Exp Eye Res 203:108424 |
| abstractText | Chronic oxidative stress and immune dysregulation are key mechanisms involved in the pathogenesis of most retinal degenerative diseases, including age-related macular degeneration. The Ccl2(-/-)/Cx3cr1(-/-)/Crb1(rd8/rd8) mouse model develops a progressive degeneration phenotype, with photoreceptor atrophy, drusen-like lesions or pigment alterations at an early age; however, the role of oxidative stress and immune function in the pathogenesis of the model is poorly understood. We performed a comprehensive characterization of the Ccl2(-/-)/Cx3cr1(-/-)/Crb1(rd8/rd8) mouse to evaluate how these pathways influence pathogenesis. We generated a Ccl2(-/-)/Cx3cr1(-/-) double-knockout (DKO) mouse on a C57BL/6N background (with the rd8 mutation of the Crb1 gene), assessed its retina status and function during 9 months in both in vivo and post-mortem analysis, and performed a comprehensive transcriptomic analysis. DKOrd8 mice presented focal retinal lesions with increased infiltration of microglia and involvement of Muller cells. Lesions progressed to thinning of the photoreceptor nuclear layer, causing a loss in retinal function. Transcriptomics analysis revealed major differential expression of genes involved in oxidative stress and neuronal function, in particular genes related to the mitochondrial electron transport chain and antioxidant cellular response. Our results suggest that alterations in chemokine signaling combined with the rd8 mutation in Ccl2(-/-)/Cx3cr1(-/-)/Crb1(rd8/rd8) mice involve early changes in several pathways associated with age-related macular degeneration, highlighting the relevance of these processes in the pathological retinal degeneration in the DKOrd8 model. |
