Mobilizing Endogenous Stem Cells for Retinal Repair

Yu, Honghua; Talib, Mays; Vu, T. H. Khanh; Cho, Kin‐Sang; Guo, Chin-Lin; Chen, Dong F.

doi:10.1016/b978-0-12-800548-4.00020-6

Cited by 7 publications

(8 citation statements)

References 131 publications

(97 reference statements)

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“…In addition, the percentage of cells with positive expression of Rhodopsin in Otx2 group was significantly higher than the percentage of cells with positive expression of EGFP, indicating that some of photoreceptor‐like cells were derived from the differentiation of transplanted cells while others may be because of the differentiation of endogenous retinal stem cells. Our observation of the spontaneous ability of MC‐RSCs to differentiate into photoreceptor‐like cells is consistent with previous report that endogenous stem cells may be activated to promote their differentiation into photoreceptor cells upon the damage of the retina …”

Section: Discussionsupporting

confidence: 92%

Otx2 enhances transdifferentiation of Müller cells‐derived retinal stem cells into photoreceptor‐like cells

Xiong

You

et al. 2018

J Cellular Molecular Medi

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Retinal Müller glial cells have the potential of neurogenic retinal progenitor cells, and could reprogram into retinal‐specific cell types such as photoreceptor cells. How to promote the differentiation of Müller cells into photoreceptor cells represents a promising therapy strategy for retinal degeneration diseases. This study aimed to enhance the transdifferentiation of rat Müller cells‐derived retinal stem cells (MC‐RSCs) into photoreceptor‐like cells and explore the signalling mechanism. We dedifferentiated rat Müller cells into MC‐RSCs which were infected with Otx2 overexpression lentivirus or control. The positive rate of photoreceptor‐like cells among MC‐RSCs treated with Otx2 overexpression lentivirus was significantly higher compared to control. Furthermore, pre‐treatment with Crx siRNA, Nrl siRNA, or GSK‐3 inhibitor SB‐216763 reduced the positive rate of photoreceptor‐like cells among MC‐RSCs treated with Otx2 overexpression lentivirus. Finally, Otx2 induced photoreceptor precursor cells were injected into subretinal space of N‐methyl‐N‐nitrosourea induced rat model of retinal degeneration and partially recovered retinal degeneration in the rats. In conclusion, Otx2 enhances transdifferentiation of MC‐RSCs into photoreceptor‐like cells and this is associated with the inhibition of Wnt signalling. Otx2 is a potential target for gene therapy of retinal degenerative diseases.

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Section: Discussionsupporting

confidence: 92%

Otx2 enhances transdifferentiation of Müller cells‐derived retinal stem cells into photoreceptor‐like cells

Xiong

You

et al. 2018

J Cellular Molecular Medi

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“…Wnt may stimulate MC proliferation through activation of the Wnt-Lin28-let7 pathway, as it was seen in the injury models [48,49]. It is likely that when MCs exhibit progenitor-like cell properties, they function as a transient intermediary entity that supports the survival and function of retinal cells to improve vision [50]. The increased progenitor cell markers can also be explained in part by the ES-induced downregulation of Notch1 and Hes1 in MCs.…”

Section: Discussionmentioning

confidence: 93%

Electrical Stimulation Induces Retinal Müller Cell Proliferation and Their Progenitor Cell Potential

Enayati

Chang

Achour

et al. 2020

Cells

Self Cite

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Non-invasive electrical stimulation (ES) is increasingly applied to improve vision in untreatable eye conditions, such as retinitis pigmentosa and age-related macular degeneration. Our previous study suggested that ES promoted retinal function and the proliferation of progenitor-like glial cells in mice with inherited photoreceptor degeneration; however, the underlying mechanism remains obscure. Müller cells (MCs) are thought to be dormant residential progenitor cells that possess a high potential for retinal neuron repair and functional plasticity. Here, we showed that ES with a ramp waveform of 20 Hz and 300 µA of current was effective at inducing mouse MC proliferation and enhancing their expression of progenitor cell markers, such as Crx (cone–rod homeobox) and Wnt7, as well as their production of trophic factors, including ciliary neurotrophic factor. RNA sequencing revealed that calcium signaling pathway activation was a key event, with a false discovery rate of 5.33 × 10−8 (p = 1.78 × 10−10) in ES-mediated gene profiling changes. Moreover, the calcium channel blocker, nifedipine, abolished the observed effects of ES on MC proliferation and progenitor cell gene induction, supporting a central role of ES-induced Ca2+ signaling in the MC changes. Our results suggest that low-current ES may present a convenient tool for manipulating MC behavior toward neuroregeneration and repair.

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“…18 Stem cell engineering has emerged as a promising approach for retinal regeneration therapy. 19,20 By incorporating stem cells into the retina and inducing their proliferation and differentiation into target cells, it is possible to replenish retinal neurons and restore retinal function. Retinal Mü ller cells, the glial cells in the retina, retain proliferation potential and offer an abundant source for cell engineering.…”

Section: Discussionmentioning

confidence: 99%

Atoh7 promotes the differentiation of Müller cells-derived retinal stem cells into retinal ganglion cells in a rat model of glaucoma

Song

Zhang

Xia

2015

Exp Biol Med (Maywood)

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Glaucoma is one of the leading eye diseases resulting in blindness due to the death of retinal ganglion cells. This study aimed to develop novel protocol to promote the differentiation of retinal Mü ller cells into ganglion cells in vivo in a rat model of glaucoma. The stem cells dedifferentiated from rat retinal Mü ller cells were randomized to receive transfection with empty lentivirus PGC-FU-GFP or lentivirus PGC-FU-Atoh7-GFP, or no transfection. The stem cells were induced further to differentiate. Ocular hypertension was induced using laser photocoagulation. The eyes were injected with Atoh7 expression vector lentivirus PGC-FU-Atoh7-GFP. Eyeball frozen sections, immunohistochemistry, RT-PCR, Western bolt, and apoptosis assay were performed. We found that the proportion of ganglion cells differentiated from Atoh7-tranfected stem cells was significantly higher than that of the other two groups. The mean intraocular pressure of glaucomatous eyes was elevated significantly compared with those of contralateral eyes. Some retinal Mü ller cells in the inner nuclear layer entered the mitotic cell cycle in rat chronic ocular hypertension glaucoma model. Atoh7 contributes to the differentiation of retinal Mü ller cells into retinal ganglion cells in rat model of glaucoma. In conclusion, Atoh7 promotes the differentiation of Mü ller cells-derived retinal stem cells into retinal ganglion cells in a rat model of glaucoma, thus opening up a new avenue for gene therapy and optic nerve regeneration in glaucoma.

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Mobilizing Endogenous Stem Cells for Retinal Repair

Cited by 7 publications

References 131 publications

Otx2 enhances transdifferentiation of Müller cells‐derived retinal stem cells into photoreceptor‐like cells

Otx2 enhances transdifferentiation of Müller cells‐derived retinal stem cells into photoreceptor‐like cells

Electrical Stimulation Induces Retinal Müller Cell Proliferation and Their Progenitor Cell Potential

Atoh7 promotes the differentiation of Müller cells-derived retinal stem cells into retinal ganglion cells in a rat model of glaucoma

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