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Ryutaro Akiba, Take Matsuyama, Hung-Ya Tu, Tomoyo Hashiguchi, Sho Junki, Shuichi Yamamoto, Yasuhiko Tabata, Masayo Takahashi, Michiko Mandai; Effect of ambient light and BDNF on photoreceptor synaptogenesis after mouse ESC/iPSC-derived retinal organoid transplantation. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3928.
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We have previously shown that stem cell-derived retinal organoid can form synapses after transplantation to end-stage retinal degeneration rd1 mouse (Akiba, et al., IOVS, 2018). However, as synapse formation is often limited, additional factors may be able to enhance synapse formation after transplantation. Here we tested whether ambient light condition and Brain Derived Neurotrophic Factor (BDNF) have effect on synaptogenesis after mouse ESC/iPSC-derived retinal organoid (mESC/iPSC-retina) transplantation to rd1 mice.
mESC/iPSC-retina were prepared as previously described (Mandai, et al., Stem Cell Rep, 2017). Subretinal injections of mESC/iPSC-retina were carried out to 7-9 weeks old rd1 mice. Transplantations were done with or without 2µg BDNF/eye that were pre-incubated with gelatin-hydrogel for controlled release. Mice without BDNF injection were reared either on cyclic light (LD) condition or constant dark (DD) condition to investigate the effect of ambient light. Mice were sacrificed 30 days after transplantation, and eyes were enucleated for immunohistochemistry characterization of synapses. rd1 mice without transplantation were also sampled for comparison. The number and degree of maturation of photoreceptor synapses were carried out using QUANTOS, a synapse evaluation method we have previously introduced (Akiba, et al., IOVS, 2018).
The number of synapses were significantly increased in all three groups (BDNF, LD, DD) when compared to rd1 without transplantation. BDNF and LD group had significantly higher numbers of synapses compared to DD condition. Also, the maturation of the synapse was enhanced when compared to rd1 mice without transplantation. While the number of synapses were very similar between BDNF and LD groups, BDNF treated group tended to exhibit more mature features.
Light has a positive effect on photoreceptor synaptogenesis after mESC/iPSC-retina transplantation. BDNF may aid photoreceptor synapse maturation.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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