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

Song, Wook; Zhang, Xueyong; Xia, Xiaobo

doi:10.1177/1535370214560965

Cited by 28 publications

(21 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Glaucoma is an eye disease characterized by optic atrophy and visual field loss and has become a major disease that affects/ human life, which could result in blindness because of the death of RGCs [23, 24]. Presently, although surgery or drugs are often used to control IOP, patients with controlled IOP still suffer from optic atrophy and RGC apoptosis [25, 26].…”

Section: Discussionmentioning

confidence: 99%

Long Non-Coding RNA-MALAT1 Mediates Retinal Ganglion Cell Apoptosis Through the PI3K/Akt Signaling Pathway in Rats with Glaucoma

You

et al. 2017

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

Background/Aims: The aim of the present study is to investigate the effect of long non-coding RNA-MALAT1 (LncRNA-MALAT1) on retinal ganglion cell (RGC) apoptosis mediated by the PI3K/Akt signaling pathway in rats with glaucoma. Methods: RGCs were isolated and cultured, and monoclonal antibodies (anti-rat Thy-1, Brn3a and RBPMS) were examined by immunocytochemistry. An overexpression vector MALAT1-RNA activation (RNAa), gene knockout vector MALAT1-RNA interference (RNAi), and control vector MALAT1-negative control (NC) were constructed. A chronic high intraocular pressure (IOP) rat model of glaucoma was established by episcleral vein cauterization. The RGCs were divided into the RGC control, RGC pressure, RGC pressure + MALAT1-NC, RGC pressure + MALAT1-RNAi and RGC pressure + MALAT1-RNAa groups. Sixty Sprague-Dawley (SD) rats were randomly divided into the normal, high IOP, high IOP + MALAT1-NC, high IOP + MALAT1-RNAa and high IOP + MALAT1-RNAi groups. qRT-PCR and western blotting were used to detect the expression levels of LncRNA-MALAT1 and PI3K/Akt. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and flow cytometry were used to detect RGC apoptosis. Results: Immunocytochemistry revealed that the cultured RGCs reached 90% purity. Compared with the RGC pressure + MALAT1-NC group, the RGC pressure + MALAT1-RNAa group exhibited elevated expression levels of MALAT1, lower total protein levels of PI3K and Akt and decreased RGC apoptosis, while these expression levels were reversed in the RGC pressure + MALAT1-RNAi group. RGC numbers and PI3K/Akt expression levels in the high IOP model groups were lower than those in the normal group. In the high IOP + MALAT1-RNAa group, the mRNA and protein expression levels of PI3K/Akt were reduced but higher than those in the other three high IOP model groups. Additionally, RGC numbers in the high IOP + MALAT1-RNAa group were lower than those in the normal group but higher than those in the other three high IOP model groups. Conclusion: Our study provides evidence that LncRNA-MALAT1 could inhibit RGC apoptosis in glaucoma through activation of the PI3K/Akt signaling pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Long Non-Coding RNA-MALAT1 Mediates Retinal Ganglion Cell Apoptosis Through the PI3K/Akt Signaling Pathway in Rats with Glaucoma

You

et al. 2017

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

show abstract

“…Müller cells can obtain retinal stem cell characteristics under specific conditions . Retinal Müller cells cultured in serum‐free medium supplemented with N2 and B27 could dedifferentiate into retinal stem cells and express stem cells marker Nestin and proliferation marker Ki‐67 .…”

Section: Discussionmentioning

confidence: 99%

“…The scotopic aand b-waves were significantly higher in MNU model rats receiving subretinal injection of lentivirus pGC-FU-Otx2-EGFP infected MC-RSCs than in MNU model rats or MNU model rats receiving subretinal injection of lentivirus pGC-FU-EGFP infected MC-RSCs (Figure 7A,B). These results suggest that photoreceptor function has better recovery after transplantation of MC-RSCs with Otx2 overexpression.4 | DISCUSSIONMüller cells can obtain retinal stem cell characteristics under specific conditions 11,23. Retinal Müller cells cultured in serum-free medium supplemented with N2 and B27 could dedifferentiate into retinal stem cells and express stem cells marker Nestin and proliferation marker Ki-67 21.…”

mentioning

confidence: 89%

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

Xiong

You

et al. 2018

J Cellular Molecular Medi

View full text Add to dashboard Cite

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.

show abstract

“…The enrichment of Müller cells and differentiation into RGCs were performed as previously described [7].…”

Section: Dedifferentiation Of Purified Müller Cells Into Retinal Stemmentioning

confidence: 99%

“…The dedifferentiated retinal Müller cells then differentiate into different types of neurons such as retinal ganglion cells (RGCs). Our previous studies showed that RGCs derived from Müller cells had defects in axon growth, leading to a defect in signal conduction [6,7].…”

Section: Introductionmentioning

confidence: 99%

MiR-124 Promotes the Growth of Retinal Ganglion Cells Derived from Müller Cells

et al. 2018

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

Background/Aims: Retinal Müller cells could be induced to differentiate into retinal ganglion cells (RGCs), but RGCs derived from Müller cells have defects in axon growth, leading to a defect in signal conduction. In this study we aimed to explore the role of miR-124 in axon growth of RGCs derived from Müller cells. Methods: Müller cells were isolated from rat retina and induced to dedifferentiate into retinal stem cells. The stem cells were infected by PGC-FU-Atoh7-GFP lentivirus and then transfected with miR-124 or anti-miR-124, and the length of axon was compared. Furthermore, the cells were injected into the eyes of rat chronic ocular hypertension glaucoma model and axon growth in vivo was examined. The targeting of CoREST by miR-124 was detected by luciferase assay. Results: In retinal stem cells, the length of axon was 1,792±64.54 μm in miR-124 group, 509±21.35 μm in control group, and only 87.9±9.24 μm in anti-miR-124 group. In rat model, miR-124 promoted axon growth of RGCs differentiated from retinal stem cells. Furthermore, we found that miR-124 negatively regulated CoREST via directly targeting the binding site in CoREST 3′ UTR. Conclusions: We provide the first evidence that miR-124 regulates axon growth of RGCs derived from Müller cells, and miR-124 has translational potential for gene therapy of glaucoma.

show abstract

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

Cited by 28 publications

References 25 publications

Long Non-Coding RNA-MALAT1 Mediates Retinal Ganglion Cell Apoptosis Through the PI3K/Akt Signaling Pathway in Rats with Glaucoma

Long Non-Coding RNA-MALAT1 Mediates Retinal Ganglion Cell Apoptosis Through the PI3K/Akt Signaling Pathway in Rats with Glaucoma

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

MiR-124 Promotes the Growth of Retinal Ganglion Cells Derived from Müller Cells

Contact Info

Product

Resources

About