| First Author | Palani CD | Year | 2019 |
| Journal | Mol Neurobiol | Volume | 56 |
| Issue | 12 | Pages | 8589-8602 |
| PubMed ID | 31280447 | Mgi Jnum | J:294452 |
| Mgi Id | MGI:6456421 | Doi | 10.1007/s12035-019-01691-w |
| Citation | Palani CD, et al. (2019) Deletion of Arginase 2 Ameliorates Retinal Neurodegeneration in a Mouse Model of Multiple Sclerosis. Mol Neurobiol 56(12):8589-8602 |
| abstractText | 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 knockout (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 with WT controls. Retinal flat mount studies demonstrated a significant reduction in the number of RGCs in WT EAE retinas in comparison with normal control mice. A significant improvement in neuronal survival was evident in retinas of EAE-induced A2(-/-) mice compared with WT. RNA levels of the proinflammatory molecules CCL2, COX2, IL-1alpha, and IL-12alpha were significantly reduced in the A2(-/-) EAE retinas compared with WT EAE. EAE-induced activation of glia (microglia and Muller cells) was markedly reduced in A2(-/-) retinas compared with 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. |
