| First Author | Talla V | Year | 2020 |
| Journal | eNeuro | Volume | 7 |
| Issue | 2 | PubMed ID | 32165410 |
| Mgi Jnum | J:288482 | Mgi Id | MGI:6430046 |
| Doi | 10.1523/ENEURO.0320-19.2020 | Citation | Talla V, et al. (2020) Targeted Kruppel-Like Factor 4 Gene Knock-Out in Retinal Ganglion Cells Improves Visual Function in Multiple Sclerosis Mouse Model. eNeuro 7(2):ENEURO.0320-19.2020 |
| abstractText | Axonal demyelination injury and neuronal degeneration are the primary causes of visual disability in multiple sclerosis (MS)-linked optic neuritis patients. Immunomodulatory therapies targeting inflammation have failed to avert the disease progression and no therapies exist to prevent the neuronal deficits seen in MS to date. Neuroprotective strategies targeting oligodendrocytes and astroglia have shown limited success due to a lack of axonal regeneration from injured neurons. In this study, we used the chronic experimental autoimmune encephalomyelitis (EAE) mouse model of MS to investigate the axonal regenerative approach to improve the neuronal function. Our approach focused on targeted knock-out (KO) of the developmentally regulated axon growth inhibitory Kruppel-like factor 4 (Klf4) gene in retinal ganglion cells (RGCs) of Klf4(fl/fl) mice by intravitreal delivery of AAV2-Cre-ires-EGFP recombinant virus (1) at the time of EAE sensitization and (2) after the onset of optic neuritis-mediated visual defects in the mice. Klf4 gene KO performed simultaneous with EAE sensitization prevented the visual loss as assessed by pattern electroretinograms (PERGs) in the mice and protected the RGCs from EAE-mediated death. More importantly, however, Klf4 gene KO after the onset of optic neuritis also resulted in RGC neuroprotection with additional restoration of their function, thereby improving the visual function outcomes in the EAE model. This study establishes the efficacy of Klf4 targeted knock-down in EAE even after the onset of disease symptoms, and thus should be further explored as a potential treatment strategy for MS/optic neuritis patients. |
