Interkinetic Nuclear Migration in the Regenerating Retina

The vertebrate retina is a highly multilayered nervous tissue with a large diversity of cellular components. With the development of stem cell technologies, human retinas can be generated in three-dimensional (3-D) culture in vitro. However, understanding the factors modulating key productive processes and the way that they influence development are far from clear. Oxygen, as the most essential element participating in metabolism, is a critical factor regulating organic development. In this study, using 3-D culture of human stem cells, we examined the effect of intermittent high oxygen treatment (40% O2) on the formation and cellular behavior of neural retinas (NR) in the embryonic body (EB). The volume of EB and number of proliferating cells increased significantly under 40% O2 on day 38, 50, and 62. Additionally, the ratio of PAX6+ cells within NR was significantly increased. The neural rosettes could only develop with correct apical-basal polarity under 40% O2. In addition, the generation, migration and maturation of retinal ganglion cells were enhanced under 40% O2. All of these results illustrated that 40% O2 strengthened the formation of NR in EB with characteristics similar to the in vivo state, suggesting that the hyperoxic state facilitated the retinal development in vitro.

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“…4a–h ). These cells were undergoing interkinetic nuclear migration 33 34 and high oxygen concentrations promote this process.…”

Section: Resultsmentioning

confidence: 99%

Intermittent high oxygen influences the formation of neural retinal tissue from human embryonic stem cells

Gao

Chen

Zeng

et al. 2016

Sci Rep

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“…2) 16,17 . The significance of interkinetic nuclear migration during retina regeneration has not been studied, but may expose nuclei to a changing gradient of factors spanning the retina that impact progenitor proliferation and differentiation 18,19 .…”

Section: Müller Glia and Their Behavior In The Damaged Retinamentioning

confidence: 99%

Retina regeneration in zebrafish

Wei

Goldman

2016

Current Opinion in Genetics & Development

207

212

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Unlike mammals, zebrafish are able to regenerate a damaged retina. Key to this regenerative response are Müller glia that respond to retinal injury by undergoing a reprogramming event that allows them to divide and generate a retinal progenitor that is multipotent and responsible for regenerating all major retinal neuron types. The fish and mammalian retina are composed of similar cell types with conserved function. Because of this it is anticipated that studies of retina regeneration in fish may suggest strategies for stimulating Müller glia reprogramming and retina regeneration in mammals. In this review we describe recent advances and future directions in retina regeneration research using zebrafish as a model system.

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“…Similar to retinal progenitor cells during development, responsive Müller cells exhibit interkinetic nuclear movements, with their nuclei migrating apically to undergo mitosis (Lahne et al, 2013; Nagashima et al, 2013). Activated Müller cells undergo a single asymmetric division to self-renew and produce a proliferating retinal progenitor (Lenkowski and Raymond, 2014; Nagashima et al, 2013) (Figure 2).…”

Section: Müller Cell Response To Injury In Fishmentioning

confidence: 99%

Müller glial cell‐dependent regeneration of the neural retina: An overview across vertebrate model systems

Hamon

Roger

Yang

et al. 2016

Developmental Dynamics

110

103

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Retinal dystrophies are a major cause of blindness for which there are currently no curative treatments. Transplantation of stem cell-derived neuronal progenitors to replace lost cells has been widely investigated as a therapeutic option. Another promising strategy would be to trigger self-repair mechanisms in patients, through the recruitment of endogenous cells with stemness properties. Accumulating evidence in the last 15 years has revealed that several retinal cell types possess neurogenic potential, thus opening new avenues for regenerative medicine. Among them, Müller glial cells have been shown to be able to undergo a reprogramming process to re-acquire a stem/progenitor state, allowing them to proliferate and generate new neurons for repair following retinal damages. Although Müller cell-dependent spontaneous regeneration is remarkable in some species such as the fish, it is extremely limited and ineffective in mammals. Understanding the cellular events and molecular mechanisms underlying Müller cell activities in species endowed with regenerative capacities could provide knowledge to unlock the restricted potential of their mammalian counterparts. In this context, the present review provides an overview of Müller cell responses to injury across vertebrate model systems and summarizes recent advances in this rapidly evolving field.

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Interkinetic Nuclear Migration in the Regenerating Retina

Cited by 15 publications

References 27 publications

Intermittent high oxygen influences the formation of neural retinal tissue from human embryonic stem cells

Intermittent high oxygen influences the formation of neural retinal tissue from human embryonic stem cells

Retina regeneration in zebrafish

Müller glial cell‐dependent regeneration of the neural retina: An overview across vertebrate model systems

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