| First Author | Vacca O | Year | 2014 |
| Journal | Glia | Volume | 62 |
| Issue | 3 | Pages | 468-76 |
| PubMed ID | 24382652 | Mgi Jnum | J:207503 |
| Mgi Id | MGI:5558999 | Doi | 10.1002/glia.22617 |
| Citation | Vacca O, et al. (2014) AAV-mediated gene delivery in Dp71-null mouse model with compromised barriers. Glia 62(3):468-76 |
| abstractText | Formation and maintenance of the blood-retinal barrier (BRB) is required for proper vision and breaching of this barrier contributes to the pathology in a wide variety of retinal conditions such as retinal detachment and diabetic retinopathy. Dystrophin Dp71 being a key membrane cytoskeletal protein, expressed mainly in Muller cells, its absence has been related to BRB permeability through delocalization and down-regulation of the AQP4 and Kir4.1 channels. Dp71-null mouse is thus an excellent model to approach the study of retinal pathologies showing blood-retinal barrier permeability. We aimed to investigate the participation of Muller cells in the BRB and in the inner limiting membrane of Dp71-null mice compared with wild-type mice in order to understand how these barriers work in this model of permeable BRB. To this aim, we used an Adeno-associated virus (AAV) variant, ShH10-GFP, engineered to target Muller cells specifically. ShH10 coding GFP was introduced by intravitreal injection and Muller cell transduction was studied in Dp71-null mice in comparison to wild-type animals. We show that Muller cell transduction follows a significantly different pattern in Dp71-null mice indicating changes in viral cell-surface receptors as well as differences in the permeability of the inner limiting membrane in this mouse line. However, the compromised BRB of the Dp71-null mice does not lead to virus leakage into the bloodstream when the virus is injected intravitreally - an important consideration for AAV-mediated retinal gene therapy. |
