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Adult ciliary epithelial cells, previously identified as retinal stem cells with potential for retinal repair, fail to differentiate into new rod photoreceptors

Adult ciliary epithelial cells, previously identified as retinal stem cells with potential for retinal repair, fail to differentiate into new rod photoreceptors
Adult ciliary epithelial cells, previously identified as retinal stem cells with potential for retinal repair, fail to differentiate into new rod photoreceptors
The ciliary margin in lower vertebrates is a site of continual retinal neurogenesis and a stem cell niche. By contrast, the human eye ceases retinal neuron production before birth and loss of photoreceptors during life is permanent and a major cause of blindness. The discovery of a proliferative cell population in the ciliary epithelium (CE) of the adult mammalian eye, designated retinal stem cells, raised the possibility that these cells could help to restore sight by replacing lost photoreceptors. We previously demonstrated the feasibility of photoreceptor transplantation using cells from the developing retina. CE cells could provide a renewable source of photoreceptors for transplantation. Several laboratories reported that these cells generate new photoreceptors, whereas a recent report questioned the existence of retinal stem cells. We used Nrl.gfp transgenic mice that express green fluorescent protein in rod photoreceptors to assess definitively the ability of CE cells to generate new photoreceptors. We report that CE cells expanded in monolayer cultures, lose pigmentation, and express a subset of eye field and retinal progenitor cell markers. Simultaneously, they continue to express some markers characteristic of differentiated CE and typically lack a neuronal morphology. Previously reported photoreceptor differentiation conditions used for CE cells, as well as conditions used to differentiate embryonic retinal progenitor cells (RPCs) and embryonic stem cell-derived RPCs, do not effectively activate the Nrl-regulated photoreceptor differentiation program. Therefore, we conclude that CE cells lack potential for photoreceptor differentiation and would require reprogramming to be useful as a source of new photoreceptors.
Adult Stem Cells/cytology, Animals, Basic-Leucine Zipper Transcription Factors/genetics, Cell Differentiation, Cell Proliferation, Cells, Cultured, Eye Proteins/genetics, Humans, Mice, Mice, Transgenic, Retina/cytology, Retinal Rod Photoreceptor Cells/cytology
1066-5099
1048-59
Gualdoni, Sara
d683d21a-fbc2-4fc3-a292-dc709a96e28a
Baron, Michael
37b594aa-3b71-4ff7-9edf-06e8276ce60c
Lakowski, Jorn
1856e739-982a-412a-87c7-abf1610f5384
Decembrini, Sarah
92766b9c-f219-496d-8159-b21c7552d146
Smith, Alexander J.
c563d9b8-d59d-4367-9fb4-328d350dd7d8
Pearson, Rachael A.
4b8c2476-e361-42e4-a4cb-71208646d06a
Ali, Robin R.
bddfdcbe-75ce-4264-80cc-c9ef1d6c9d7d
Sowden, Jane C.
6f414289-9a33-42ad-a3cd-2fa828b7ac27
Gualdoni, Sara
d683d21a-fbc2-4fc3-a292-dc709a96e28a
Baron, Michael
37b594aa-3b71-4ff7-9edf-06e8276ce60c
Lakowski, Jorn
1856e739-982a-412a-87c7-abf1610f5384
Decembrini, Sarah
92766b9c-f219-496d-8159-b21c7552d146
Smith, Alexander J.
c563d9b8-d59d-4367-9fb4-328d350dd7d8
Pearson, Rachael A.
4b8c2476-e361-42e4-a4cb-71208646d06a
Ali, Robin R.
bddfdcbe-75ce-4264-80cc-c9ef1d6c9d7d
Sowden, Jane C.
6f414289-9a33-42ad-a3cd-2fa828b7ac27

Gualdoni, Sara, Baron, Michael, Lakowski, Jorn, Decembrini, Sarah, Smith, Alexander J., Pearson, Rachael A., Ali, Robin R. and Sowden, Jane C. (2010) Adult ciliary epithelial cells, previously identified as retinal stem cells with potential for retinal repair, fail to differentiate into new rod photoreceptors. Stem Cells, 28 (6), 1048-59. (doi:10.1002/stem.423).

Record type: Article

Abstract

The ciliary margin in lower vertebrates is a site of continual retinal neurogenesis and a stem cell niche. By contrast, the human eye ceases retinal neuron production before birth and loss of photoreceptors during life is permanent and a major cause of blindness. The discovery of a proliferative cell population in the ciliary epithelium (CE) of the adult mammalian eye, designated retinal stem cells, raised the possibility that these cells could help to restore sight by replacing lost photoreceptors. We previously demonstrated the feasibility of photoreceptor transplantation using cells from the developing retina. CE cells could provide a renewable source of photoreceptors for transplantation. Several laboratories reported that these cells generate new photoreceptors, whereas a recent report questioned the existence of retinal stem cells. We used Nrl.gfp transgenic mice that express green fluorescent protein in rod photoreceptors to assess definitively the ability of CE cells to generate new photoreceptors. We report that CE cells expanded in monolayer cultures, lose pigmentation, and express a subset of eye field and retinal progenitor cell markers. Simultaneously, they continue to express some markers characteristic of differentiated CE and typically lack a neuronal morphology. Previously reported photoreceptor differentiation conditions used for CE cells, as well as conditions used to differentiate embryonic retinal progenitor cells (RPCs) and embryonic stem cell-derived RPCs, do not effectively activate the Nrl-regulated photoreceptor differentiation program. Therefore, we conclude that CE cells lack potential for photoreceptor differentiation and would require reprogramming to be useful as a source of new photoreceptors.

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More information

Accepted/In Press date: 11 March 2010
Published date: 28 June 2010
Keywords: Adult Stem Cells/cytology, Animals, Basic-Leucine Zipper Transcription Factors/genetics, Cell Differentiation, Cell Proliferation, Cells, Cultured, Eye Proteins/genetics, Humans, Mice, Mice, Transgenic, Retina/cytology, Retinal Rod Photoreceptor Cells/cytology

Identifiers

Local EPrints ID: 431142
URI: http://eprints.soton.ac.uk/id/eprint/431142
ISSN: 1066-5099
PURE UUID: dfa13c23-8d9a-41a7-ae31-a9e3f0de07f5
ORCID for Jorn Lakowski: ORCID iD orcid.org/0000-0003-4214-7580

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Date deposited: 24 May 2019 16:30
Last modified: 16 Mar 2024 04:33

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Contributors

Author: Sara Gualdoni
Author: Michael Baron
Author: Jorn Lakowski ORCID iD
Author: Sarah Decembrini
Author: Alexander J. Smith
Author: Rachael A. Pearson
Author: Robin R. Ali
Author: Jane C. Sowden

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