Deletion of Arginase 2 Ameliorates Retinal Neurodegeneration in a Mouse Model of Multiple Sclerosis
| Autor: | Abdelrahman Y. Fouda, Fang Liu, Sylvia B. Smith, Shailedra Giri, Chithra D. Palani, Eslam Mohamed, Zhimin Xu, Ruth B. Caldwell, S. Priya Narayanan |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Retinal Ganglion Cells medicine.medical_specialty Encephalomyelitis Autoimmune Experimental Multiple Sclerosis Neuroscience (miscellaneous) CCL2 Motor Activity Retinal ganglion Article 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Animals Retinal thinning Inflammation Retina Microglia Arginase business.industry Neurodegeneration Experimental autoimmune encephalomyelitis Retinal Degeneration Retinal medicine.disease Up-Regulation Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure Endocrinology Neurology chemistry Female sense organs business Neuroglia 030217 neurology & neurosurgery Gene Deletion Signal Transduction |
| Zdroj: | Mol Neurobiol |
| ISSN: | 1559-1182 |
| Popis: | Optic neuritis is a major clinical feature of multiple sclerosis (MS), and can lead to temporary or permanent vision loss. Previous studies from our laboratory have demonstrated the critical involvement of arginase 2 (A2) in retinal neurodegeneration in models of ischemic retinopathy. The current study was undertaken to investigate the role of A2 in MS-mediated retinal neuronal damage and degeneration. Experimental autoimmune encephalomyelitis (EAE) was induced in wild type (WT) and A2 knock out (A2(−/−)) mice. EAE-induced motor deficits, loss of retinal ganglion cells, retinal thinning, inflammatory signaling and glial activation were studied in EAE-treated WT and A2(−/−) mice and their respective controls. Increased expression of A2 was observed in WT retinas in response to EAE induction. EAE-induced motor deficits were markedly reduced in A2(−/−) mice compared to WT controls. Retinal flat mount studies demonstrated a significant reduction in the number of RGCs in WT EAE retinas in comparison to normal control mice. A significant improvement in neuronal survival was evident in retinas of EAE-induced A2(−/−) mice compared to WT. RNA levels of the proinflammatory molecules CCL2, COX2, IL-1α, and IL-12α were significantly reduced in the A2(−/−) EAE retinas compared to WT EAE. EAE-induced activation of glia (microglia and Müller cells) were markedly reduced in A2(−/−) retinas compared to WT. Western blot analyses showed increased levels of phospho-ERK1/2 and reduced levels of phospho-BAD in the WT EAE retina, while these changes were prevented in A2(−/−) mice. In conclusion, our studies establish EAE as an excellent model to study MS-mediated retinal neuronal damage and suggest the potential value of targeting A2 as a therapy to prevent MS-mediated retinal neuronal injury. |
| Databáze: | OpenAIRE |
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