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Retinal Progenitor Cells in Regeneration and Repair Highlight New Therapeutic Targets
Table 1: Cell Surface Markers Used to Identify Stem or Progenitor Cells
Marker Properties and Cell Expression Expression in Posterior Segment
A2B5 Cell surface ganglioside. Expressed on developing thymic Retinal neurones.
epithelial cells, bone marrow mesenchymal cells, NPCs,
oligodendrocyte progenitor cells and neuroendocrine cells.
ABCG2 (ATP-binding cassette superfamily Excludes DNA-intercalating dyes. Determinant of Retinal stem cells, influencing G member 2)
Hoescht-dye negative-side population cells. Present in HSCs lineage commitment.
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and committed HPCs. Good potential positive marker for
adult progenitors from multiple sources.
AC133 antigen, CD133, prominin-1, prominin-2, Pentaspan membrane glycoprotein present on many Enriches retinal progenitor cells.
prominin family types of stem and progenitor cell in human and Photoreceptor cell outer segments.
other species.
CD34 Heavily glycosylated cell surface molecule with multiple Retinal vascular endothelium, endothelial
epitopes. Expressed on HSCs/progenitor cells, as well as progenitor cells, dendritic cells, myeloid
many acute leukaemias and neoplasms of vascular origin. cells (including mast cells).
CD43 Mucin-like transmembrane sialo-glyco-protein adhesion Lymphocytes, neutrophils, monocytes
molecule. High expression on HPCs (possibly regulates and platelets. Retinal lymphoma.
proliferation) and also on mature blood cells (lymphocytes,
neutrophils, monocytes and platelets), but not on
non-haematopoietic cells.
CD45 Transmembrane tyrosine phosphatase involved in Microglia, dendritic cells of iris, ciliary
lymphocyte activation and differentiation. Expressed on body and choroid. Pericytes and early
all nucleated haematopoietic lineage cells and mature HSCs. progenitor endothelial cells.
CUB-domain-binding protein 1 (CDCP1) Transmembrane protein – cadherin family. Expressed RPE. Mutations associated with
on CD34
+
and CD133
+
HSCs, as well as metastatic tumours juvenile macular dystrophy.
(colon and breast), mesenchymal stem cells and NPCs.
c-Kit/CD117 HSC. CD117+ generates RPE when transplanted.
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Endomucin CD-34-like sialo-mucin. Expressed on HSCs throughout Present in adult and developing choroidal
development, as well as early endothelium. and retinal vessels. Present around
photoreceptors in developing retina.
Foetal liver kinase-2 (Flk-2), CD135, Stimulates proliferation of stem cells and differentiation of Expressed in all layers of the neural retina.
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fms-like tyrosine kinase receptor-3 (flt-3) lymphoid progenitor lineages. Expressed on HSCs.
Stem cell antigen 1 (Sca1) Type V glyco-phosphatidyl-inositol anchored cell surface Marrow-derived cells of this lineage
proteins, upregulated on cell activation. Expressed on give rise to retinal vessels
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and RPE.
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multipotent HSCs/progenitor cells in bone marrow.
Thy-1/CD90 Expressed on CD34
+
HPCs (with high proliferative Retinal ganglion cell neurones.
potential) and primitive cord blood progenitors, possibly
mediating a negative signal that results in inhibition of
primitive cell proliferation.
O4 Earliest marker of cells of oligodendrocyte lineage. Cultured retinal progenitor cells
(unpublished observations).
Growth factor receptors Including FGFR-1, EGFR, PDGF-αR and SCGF. Multiple on retinal neurones, endothelia,
glia, microglia, lymphocytes and RPE.
Cell surface markers are useful for isolating stem/progenitor cells. Intracellular markers are useful for characterising cells and identifying them in tissue sections, but are not used in
antibody-mediated methods of live cell separation. Using growth factor receptors to sort cells with specific antibody binding has the complication that these antibodies may then inhibit
or stimulate that receptor and so may have a functional effect.
ATP = adenosine triphosphate; EGFR = epidermal growth factor receptor; FGFR-1 = fibroblast growth factor-1; HPC = haematopoietic progenitor cell; HSC = haematopoietic stem cell;
NPC = neural progenitor cell; PDGF = platelet-derived growth factor; RPE = retinal pigment epithelium; SCGF = stem cell growth factor.
functional loss. In this context, neuroprotection involves the connections are less well established within a tissue? This would
prevention of apoptosis. If we accept that some cellular replacement certainly explain the sudden functional loss that is manifest in some
occurs, degeneration becomes a product of the relative rate of cell degenerative diseases. Treatments that protect cells from apoptosis
loss and the rate of (and potential for) cellular replacement; if deficits are as likely to work on older cells as on those that have been more
in cell replacement occur, the functional result is cellular degeneration. recently laid down. Mouse or human bone-marrow-derived stem cells
In the normal adult retina the few proliferating cells observed (of injected into mouse eyes undergoing retinal degeneration attenuate
neural, glial or vascular lineage) are principally non-myeloid, as the retinal photoreceptor degeneration and loss of vasculature and alter
majority of retinal microglia/macrophages that are replaced do not electroretinograms, although they lead to a predominance of cone
proliferate in situ.
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However, in transplant chimaeras, marrow-derived instead of rod photoreceptors.
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Cell transplants have multiple
cells home to damaged areas in the eye and regenerate retinal potential effects. In animal models, rescue of degeneration occurs by
pigment epithelium (RPE)
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as well as retinal vessels.
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cell, matrix or growth factors, suggesting that degeneration occurs
because of defects in any of these elements. Indirect evidence for this
In animal models of inherited retinal degeneration, retinal comes from RCS rats, where a defective gene (Mertk) expressed in the
degeneration is usually the result of apoptosis due to a gene deficit.
33,34
RPE for phagocytic function causes photoreceptor degeneration to
Are replacement cells more vulnerable to apoptosis because their occur. Degeneration can be delayed by retinal haemorrhage, trauma or
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