Dataset Information

Neurofascin Is a Novel Component of Rod Photoreceptor Synapses in the Outer Retina.

ABSTRACT: Neural circuit formation is an intricate and complex process where multiple neuron types must come together to form synaptic connections at a precise location and time. How this process is orchestrated during development remains poorly understood. Cell adhesion molecules are known to play a pivotal role in assembling neural circuits. They serve as recognition molecules between corresponding synaptic partners. In this study, we identified a new player in assembling neural circuits in the outer retina, the L1-family cell adhesion molecule Neurofascin (Nfasc). Our data reveals Nfasc is expressed in the synaptic layer where photoreceptors make synaptic connections to their respective partners. A closer examination of Nfasc expression shows high levels of expression in rod bipolars but not in cone bipolars. Disruption of Nfasc using a conditional knockout allele results in selective loss of pre- and post-synaptic proteins in the rod synaptic layer but not in the cone synaptic layer. Electron microscopic analysis confirms that indeed there are abnormal synaptic structures with less dendrites of rod bipolars innervating rod terminals in loss of Nfasc animals. Consistent with these findings, we also observe a decrease in rod-driven retinal responses with disruption of Nfasc function but not in cone-driven responses. Taken together, our data suggest a new role of Nfasc in rod synapses within the mouse outer retina.

SUBMITTER: Pourhoseini S

PROVIDER: S-EPMC7902911 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Vectors based on the adeno-associated virus (AAV) are currently the preferred tools for delivering genes to photoreceptors (PR) in small and large animals. AAVs have been applied successfully in various models of PR dystrophies. However, unknown barriers still limit AAV's efficient application in several forms of severe PR degenerations due to insufficient transgene expression and/or treated cells at the time of injection. Optimizations of PR gene therapy strategies will likely benefit from the identification of the cellular factors that influence PR transduction. Interestingly, recent studies have shown that the AAV transduction profile of PRs differs significantly between neonatal and adult mouse retinas after subretinal injection. This phenomenon may provide clues to identify host factors that influence the efficiency of AAV-mediated PR transduction. This study demonstrates that rod outer segments are critical modulators of efficient AAV-mediated rod transduction. During retinal development, rod transduction correlated temporally and spatially with the differentiation order of PRs when vectors were introduced subretinally but not when introduced intravitreally. All subretinally injected vectors had an initial preference to transduce cones in the absence of formed rod outer segments and then displayed a preference for rods as the cells matured, independently of the expression cassette or AAV serotype. Consistent with this observation, altered development of rod outer segments was associated with a strong reduction of rod transduction and an increase in the percentage of transduced cones by 2- to 2.8-fold. A similar increase of cone transduction was observed in the adult retinal degeneration 1 (rd1) retina compared to wild-type mice. These results suggest that the loss of rod outer segments in diseased retinas could markedly affect gene transfer efficiency of AAV vectors by limiting the ability of AAVs to infect dying rods efficiently. This information could be exploited for the development of more efficient AAV-based PR gene delivery procedures.

Dataset Information

Neurofascin Is a Novel Component of Rod Photoreceptor Synapses in the Outer Retina.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets