| First Author | Laird JG | Year | 2019 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 60 |
| Issue | 8 | Pages | 3150-3161 |
| PubMed ID | 31335952 | Mgi Jnum | J:277445 |
| Mgi Id | MGI:6331476 | Doi | 10.1167/iovs.19-27226 |
| Citation | Laird JG, et al. (2019) Rescue of Rod Synapses by Induction of Cav Alpha 1F in the Mature Cav1.4 Knock-Out Mouse Retina. Invest Ophthalmol Vis Sci 60(8):3150-3161 |
| abstractText | Purpose: Cav1.4 is a voltage-gated calcium channel clustered at the presynaptic active zones of photoreceptors. Cav1.4 functions in communication by mediating the Ca2+ influx that triggers neurotransmitter release. It also aids in development since rod ribbon synapses do not form in Cav1.4 knock-out mice. Here we used a rescue strategy to investigate the ability of Cav1.4 to trigger synaptogenesis in both immature and mature mouse rods. Methods: In vivo electroporation was used to transiently express Cav alpha1F or tamoxifen-inducible Cav alpha1F in a subset of Cav1.4 knock-out mouse rods. Synaptogenesis was assayed using morphologic markers and a vision-guided water maze. Results: We found that introduction of Cav alpha1F to knock-out terminals rescued synaptic development as indicated by PSD-95 expression and elongated ribbons. When expression of Cav alpha1F was induced in mature animals, we again found restoration of PSD-95 and elongated ribbons. However, the induced expression of Cav alpha1F led to diffuse distribution of Cav alpha1F in the terminal instead of being clustered beneath the ribbon. Approximately a quarter of treated animals passed the water maze test, suggesting the rescue of retinal signaling in these mice. Conclusions: These data confirm that Cav alpha1F expression is necessary for rod synaptic terminal development and demonstrate that rescue is robust even in adult animals with late stages of synaptic disease. The degree of rod synaptic plasticity seen here should be sufficient to support future vision-restoring treatments such as gene or cell replacement that will require photoreceptor synaptic rewiring. |
