PURPOSE. To establish a model of the retinal capillary circulation in pigs, which in many aspects is close to the human retina.METHODS. Using high density confocal microscopy image stacks of immunolabeled porcine retinal whole mounts, microvessels close to the optic nerve head were traced in three dimensions. The direction of flow of individual capillaries was deduced from their arteriolar and/or venous connections.RESULTS. From major arteries, second-order arteries traversed the nerve fiber layer and resolved exclusively into the superficial vascular plexus (SVP), which dichotomized the blood flow between radial peripapillary capillaries (RPCs) on one side and the intermediate (IVP) and deep vascular plexus (DVP) on the other. Each RPC was supplied by one or several capillaries from the SVP and drained to the IVP or DVP. The DVP was a mosaic of approximately 300 to 600 lm wide anastomotic watersheds, each drained by one or two venules connected to major veins. A presumptive direction of flow could be determined for >90% of capillaries. These results suggest a model of the capillary circulation in which the three microvessel layers are serially organized with RPCs are in parallel between the SVP and IVP or DVP.CONCLUSIONS. In the peripapillary retina of pigs, microvascular layers have a serial arrangement, with RPCs emerging from the SVP and draining to the IVP or DVP; hence, connected in parallel of this scheme. The bulk of flow, therefore, traverses the SVP and DVP successively. This organization contributes to the higher oxygen saturation in the SVP and RPCs than in the DVP. Physiopathologic implications of this model regarding retinal diseases are discussed.

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 Müller 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 Müller 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 Müller cells specifically. ShH10 coding GFP was introduced by intravitreal injection and Müller cell transduction was studied in Dp71‐null mice in comparison to wild‐type animals. We show that Müller 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. GLIA 2014;62:468–476