The ciliary marginal zone (CMZ) in development and regeneration of the vertebrate eye

Fischer, Andy J.; Bosse, Jennifer L.; El‐Hodiri, Heithem M.

doi:10.1016/j.exer.2013.08.018

Cited by 77 publications

(73 citation statements)

References 60 publications

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“…Another kind of progenitor is located at the peripheral margin of the NR, the ciliary margin (CM) 5,10,11 . The teleost (fish) eye contains an active stem cell system in the CM zone (also called circumferential germinal zone) that contributes to NR expansion by de novo generation of the tissue even in adulthood 12 .…”

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confidence: 99%

Generation of a ciliary margin-like stem cell niche from self-organizing human retinal tissue

et al. 2015

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In the developing neural retina (NR), multipotent stem cells within the ciliary margin (CM) contribute to de novo retinal tissue growth. We recently reported the ability of human embryonic stem cells (hESCs) to self-organize stratified NR using a three-dimensional culture technique. Here we report the emergence of CM-like stem cell niches within human retinal tissue. First, we developed a culture method for selective NR differentiation by timed BMP4 treatment. We then found that inhibiting GSK3 and FGFR induced the transition from NR tissue to retinal pigment epithelium (RPE), and that removing this inhibition facilitated the reversion of this RPE-like tissue back to the NR fate. This step-wise induction-reversal method generated tissue aggregates with RPE at the margin of central-peripherally polarized NR. We demonstrate that the NR-RPE boundary tissue further self-organizes a niche for CM stem cells that functions to expand the NR peripherally by de novo progenitor generation.

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confidence: 99%

Generation of a ciliary margin-like stem cell niche from self-organizing human retinal tissue

et al. 2015

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“…In line with a prominent expression of megalin in stem cell-like cytotrophoblasts, megalin expression was likewise recently described in the ocular ciliary marginal zone of mice 50 which holds undifferentiated retinal stem and progenitor cells in vertebrates. 51 Here, megalin has been proposed to modulate sonic hedgehog signaling during embryonic development. 50 Megalin has furthermore been identified in the subependymal zone of the lateral ventricles in adult brain and to modulate bone morphogenetic protein 4 signaling in these cells.…”

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confidence: 99%

Megalin Is Predominantly Observed in Vesicular Structures in First and Third Trimester Cytotrophoblasts of the Human Placenta

Storm

Christensen

et al. 2016

J Histochem Cytochem.

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SummaryThe membrane receptor megalin is crucial for normal fetal development. Besides its expression in the developing fetus, megalin is also expressed in the human placenta. Similar to its established function in the kidney proximal tubules, placental megalin has been proposed to mediate uptake of vital nutrients. However, details of megalin expression, subcellular localization, and function in the human placenta remain to be established. By immunohistochemical analyses of first trimester and term human placenta, we showed that megalin is predominantly expressed in cytotrophoblasts, the highly proliferative cells in placenta. Only limited amounts of megalin could be detected in syncytiotrophoblasts and least in term placenta syncytiotrophoblasts. Immunocytochemical analyses furthermore showed that placental megalin associates with structures of the endolysosomal apparatus. Combined, our results clearly place placental megalin in the context of endocytosis and trafficking of ligands. However, due to the limited expression of megalin in syncytiotrophoblasts, especially in term placenta, it appears that the main role for placental megalin is not to mediate uptake of nutrients from the maternal bloodstream, as previously proposed. In contrast, our results point toward novel and complex functions for megalin in the cytotrophoblasts. Thus, we propose that the perception of placental megalin localization and function should be revised. (J Histochem Cytochem 64:769-784, 2016)

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“…27 The ciliary marginal zone (CMZ) is a ring of cells at the periphery of the maturing and matured neural retina that contains RSCs and progenitor cells. Retinal neurons are added to the periphery of the retina by differentiation of these nonpigmented CMZ RSCs and associated progenitor cells.…”

Section: Pigmented Ciliary Marginal Zonementioning

confidence: 99%

Retinal stem cells and potential cell transplantation treatments

Lin¹,

Hsu²,

Chien³

et al. 2014

Journal of the Chinese Medical Association

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The retina, histologically composed of ten delicate layers, is responsible for light perception and relaying electrochemical signals to the secondary neurons and visual cortex. Retinal disease is one of the leading clinical causes of severe vision loss, including age-related macular degeneration, Stargardt's disease, and retinitis pigmentosa. As a result of the discovery of various somatic stem cells, advances in exploring the identities of embryonic stem cells, and the development of induced pluripotent stem cells, cell transplantation treatment for retinal diseases is currently attracting much attention. The sources of stem cells for retinal regeneration include endogenous retinal stem cells (e.g., neuronal stem cells, Müller cells, and retinal stem cells from the ciliary marginal zone) and exogenous stem cells (e.g., bone mesenchymal stem cells, adipose-derived stem cells, embryonic stem cells, and induced pluripotent stem cells). The success of cell transplantation treatment depends mainly on the cell source, the timing of cell harvesting, the protocol of cell induction/transplantation, and the microenvironment of the recipient's retina. This review summarizes the different sources of stem cells for regeneration treatment in retinal diseases and surveys the more recent achievements in animal studies and clinical trials. Future directions and challenges in stem cell transplantation are also discussed.

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The ciliary marginal zone (CMZ) in development and regeneration of the vertebrate eye

Cited by 77 publications

References 60 publications

Generation of a ciliary margin-like stem cell niche from self-organizing human retinal tissue

Generation of a ciliary margin-like stem cell niche from self-organizing human retinal tissue

Megalin Is Predominantly Observed in Vesicular Structures in First and Third Trimester Cytotrophoblasts of the Human Placenta

Retinal stem cells and potential cell transplantation treatments

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