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Neural progenitor cell-derived neurotrophic support for the degenerating retina: an in vitro study
Linnaeus University, Faculty of Health and Life Sciences, Department of Medicine and Optometry. (Retinal research)
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Place, publisher, year, edition, pages
Växjö: Linnaeus University press , 2013. , p. 77
Series
Linnaeus University Dissertations ; 158
Keywords [en]
retinal degeneration, apoptosis, retina, ER-stress, autophagy
National Category
Natural Sciences
Research subject
Natural Science, Biomedical Sciences
Identifiers
URN: urn:nbn:se:lnu:diva-31164ISBN: 978-91-87427-67-1 (print)OAI: oai:DiVA.org:lnu-31164DiVA, id: diva2:677930
Public defence
2013-12-20, N2007, Västergård, Kalmar, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2014-02-03 Created: 2013-12-10 Last updated: 2014-02-03Bibliographically approved
List of papers
1. Autophagy en ER-stress contribute to photoreceptor degenenration in cultured adult porcine retina
Open this publication in new window or tab >>Autophagy en ER-stress contribute to photoreceptor degenenration in cultured adult porcine retina
(English)Manuscript (preprint) (Other academic)
Keywords
photoreceptors, apoptosis, autophagy, endoplasmisk reticulum stress, porcine
National Category
Ophthalmology
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-31163 (URN)
Available from: 2013-12-10 Created: 2013-12-10 Last updated: 2015-02-25Bibliographically approved
2. Further assessment of neuropathology in retinal explants and neuroprotection by human neural progenitor cells.
Open this publication in new window or tab >>Further assessment of neuropathology in retinal explants and neuroprotection by human neural progenitor cells.
2011 (English)In: Journal of Neural Engineering, ISSN 1741-2560, E-ISSN 1741-2552, Vol. 8, no 6, p. Article ID: 066012-Article in journal (Refereed) Published
Abstract [en]

Explanted rat retinas show progressive photoreceptor degeneration that appears to be caspase-12-dependent. Decrease in photoreceptor density eventually affects the inner retina, particularly in the bipolar cell population. Explantation and the induced photoreceptor degeneration are accompanied by activation of Müller and microglia cells. The goal of this study was to determine whether the presence of a feeder layer of human neural progenitor cells (hNPCs) could suppress the degenerative and reactive changes in the explants. Immunohistochemical analyses showed considerable sprouting of rod photoreceptor axon terminals into the inner retina and reduced densities of cone and rod bipolar cells. Both sprouting and bipolar cell degenerations were significantly lower in retinas cultured with feeder layer cells compared to cultured controls. A tendency toward reduced microglia activation in the retinal layers was also noted in the presence of feeder layer cells. These results indicate that hNPCs or factors produced by them can limit the loss of photoreceptors and secondary injuries in the inner retina. The latter may be a consequence of disrupted synaptic arrangement.

National Category
Natural Sciences
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-23051 (URN)10.1088/1741-2560/8/6/066012 (DOI)2-s2.0-81855200041 (Scopus ID)
Available from: 2012-12-19 Created: 2012-12-19 Last updated: 2017-12-06Bibliographically approved
3. Death of photoreceptors in organotypic retinal explant cultures: implication of rhodopsin accumulation and endoplasmic reticulum stress.
Open this publication in new window or tab >>Death of photoreceptors in organotypic retinal explant cultures: implication of rhodopsin accumulation and endoplasmic reticulum stress.
2011 (English)In: Journal of Neuroscience Methods, ISSN 0165-0270, E-ISSN 1872-678X, ISSN 0165-0270, Vol. 197, no 1, p. 56-64Article in journal (Refereed) Published
Abstract [en]

Here we suggest that endoplasmic reticulum (ER)-stress may be induced following aberrant rhodopsin accumulation in photoreceptors in explanted rat retinas. Rhodopsin accumulation was accompanied by increased phosphorylation of pancreatic ER-kinase and eukaryotic initiator factor 2α as well as increased levels of C/EBP homologous protein, glucose-regulated protein 78 and eventually increased cleaved caspase-12 and cleaved caspase-3. Glucose-regulated protein 78, pancreatic ER-kinase, caspase-12 and cleaved caspase-3 were present in photoreceptors, indicating that ER-stress and apoptosis are induced in this cell population. These results suggest that ER-stress and subsequent apoptosis is induced in healthy photoreceptors, presumably by aberrant accumulation of rhodopsin and the phosphorylation of eukaryotic initiator factor 2α. The explant culture system may allow investigations of neuroprotective strategies.

Keywords
Retina, Photoreceptor, Apoptosis, ER stress, Rhodopsin
National Category
Natural Sciences
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-23046 (URN)10.1016/j.jneumeth.2011.01.030 (DOI)2-s2.0-79953054741 (Scopus ID)
Available from: 2012-12-19 Created: 2012-12-19 Last updated: 2017-12-06Bibliographically approved
4. Human neural progenitor cells promote photoreceptor survival in retinal explants
Open this publication in new window or tab >>Human neural progenitor cells promote photoreceptor survival in retinal explants
Show others...
2010 (English)In: Experimental Eye Research, ISSN 0014-4835, E-ISSN 1096-0007, Vol. 90, no 2, p. 292-299Article in journal (Refereed) Published
Abstract [en]

Different types of progenitor and stem cells have been shown to provide neuroprotection in animal models of photoreceptor degeneration. The present study was conducted to investigate whether human neural progenitor cells (HNPCs) have neuroprotective properties on retinal explants models with calpain- and caspase-3-dependent photoreceptor cell death. In the first experiments, HNPCs in a feeder layer were co-cultured for 6 days either with postnatal rd1 mouse or normal rat retinas. Retinal histological sections were used to determine outer nuclear layer (ONL) thickness, and to detect the number of photoreceptors with labeling for calpain activity, cleaved caspase-3 and TUNEL. The ONL thickness of co-cultured rat and rd1 retinas was found to be almost 10% and 40% thicker, respectively, compared to controls. Cell counts of calpain activity, cleaved caspase-3 and TUNEL labeled photoreceptors in both models revealed a 30-50% decrease when co-cultured with HNPCs. The results represent significant increases of photoreceptor survival in the co-cultured retinas. In the second experiments, for an identification of putative survival factors, or a combination of them, a growth factor profile was performed on conditioned medium. The relative levels of various growth factors were analyzed by densitometric measurements of growth factor array membranes. Following growth factors were identified as most potential survival factors; granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GMCSF), insulin-like growth factor II (IGF-II), neurotrophic factor 3 (NT-3), placental growth factor (PIGF), transforming growth factors (TGF-beta1 and TGF-beta2) and vascular endothelial growth factor (VEGF-D). HNPCs protect both against calpain- and caspase-3-dependent photoreceptor cell death in the rd1 mouse and against caspase-3-dependent photoreceptor cell death in normal rat retinas in vitro. The protective effect is possibly achieved by a variety of growth factors secreted from the HNPCs.

Keywords
retina, photoreceptor, apoptosis, neuroprotection, progenitor cells
National Category
Natural Sciences
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-23045 (URN)10.1016/j.exer.2009.11.005 (DOI)
Funder
EU, European Research Council
Available from: 2012-12-19 Created: 2012-12-19 Last updated: 2017-12-06Bibliographically approved

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