3/18/2023 0 Comments Retina transplantsWe included non-treated rd1 ( rd1/ B6) mice as reference data (n = 11) for comparison with each mouse ( Figure 3D, black dots and curves). When the 95% credible interval of the distribution of the estimated β 3 was above zero, we judged that interference (mostly transplantation in our study) improved visual function. Among these parameters, β 3 showed the effect of interference with visual function. Thus, instead of simply accepting the avoidance rate, we included inter-trial interval (ITI) counts as an additional observation: for every tested animal, we fitted the observed results to a model with three parameters, namely β 1, β 2, and β 3, and estimated the parameters as features of the animal ( Figure S3A). ), but mice tend to move more randomly when they are not confident of avoiding the stimuli, which can increase the avoidance ratio simply by chance. We also stained one of the postsynaptic markers, CACNA1s, that was reported to localize at postsynaptic ribbon synapses and recently identified to cross-react with GRP179 ( Although it was sometimes difficult to distinguish graft and host terminals of either bipolar cells or photoreceptors, our labeling approach offers evidence of direct contact between the host L7-GFP-positive bipolar cell dendrites and tdTomato-positive graft photoreceptor synaptic terminals, such as seen between bipolar dendrites and CtBP2 in L7-GFP wild-type retina ( Figures 2B and 2C–2C‴). GFP-positive host bipolar cells sometimes extend their dendrites even through the remaining graft INL to reach tdTomato-positive graft CtBP2 ( Figure 2A ). In the L7-GFP retina, GFP-positive bipolar cells mostly overlapped with protein kinase Cα (PKCα)-positive bipolar cells, but in L7-GFP/ rd, GFP expression was reduced in variable degree in PKCα-positive cells in some parts of the retina ( Figures S2B and S2C). We then more closely studied the contact between L7-GFP-positive host bipolar cells and CtBP2-tdTomato on graft photoreceptors. We also found the outgrowth of tdTomato-positive graft CtBP2 into the host synaptic layer ( Figures 1D–1D‴, arrows). Some terminals in the host retina were negative for tdTomato ( Figure 1C, arrows), suggesting that they were the remnants of host photoreceptors. These findings indicate that tdTomato represents the CtBP2 expression at graft photoreceptor terminals. CtBP2-tdTomato also clustered at the tips of graft bipolar dendrites where they formed intra-graft synapses with Nrl-GFP-positive photoreceptors ( Figure S2A). CtBP2-tdTomato, which was present along the margins of the Nrl-GFP-positive graft ONL, colocalized with anti-CtBP2 immunostaining ( Figures 1B–1B‴). ), and L7-GFP-positive host bipolar terminals contacted CtBP2-tdTomato-positive graft regions. Our data provides a proof of concept for transplanting ESC/iPSC retinas to restore vision in end-stage retinal degeneration. In the present study, by transplanting mouse iPSC-derived retinal tissue (miPSC retina) in the end-stage retinal-degeneration model ( rd1), we visualized the direct contact between host bipolar cell terminals and the presynaptic terminal of graft photoreceptors by gene labeling, showed light-responsive behaviors in transplanted rd1 mice, and recorded responses from the host retina with transplants by ex vivo micro-electroretinography and ganglion cell recordings using a multiple-electrode array system. However, cell-based therapies for end-stage degenerative retinas that have lost the outer nuclear layer (ONL) are still a big challenge. Recent success in functional recovery by photoreceptor precursor transplantation in dysfunctional retina has led to an increased interest in using embryonic stem cell (ESC) or induced pluripotent stem cell (iPSC)-derived retinal progenitors to treat retinal degeneration.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |