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Johansson, Kjell
Publications (10 of 54) Show all publications
Mohlin, C., Taylor, L., Ghosh, F. & Johansson, K. (2014). Autophagy and ER-stress contribute to photoreceptor degeneration in cultured adult porcine retina. Brain Research, 1585, 167-183
Open this publication in new window or tab >>Autophagy and ER-stress contribute to photoreceptor degeneration in cultured adult porcine retina
2014 (English)In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1585, p. 167-183Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to investigate rod and cone photoreceptor degeneration in organotypic cultures of adult porcine retina. Our hypothesis was that the photoreceptors accumulate opsins, which, together with exposure to cyclic dim light illumination, induce autophagy and endoplasmic reticulum stress (ER-stress) to overcome damaging protein overload. For this purpose, retinas were cultured for 48 h and 72 h during which they were illuminated with dim light for 8 h/day; specimens were analyzed by means of immunohistochemistry, Western blot, real-time polymerase chain reaction (PCR) and transmission electron microscopy. ER-stress and photoreceptor degeneration was observed in conventionally cultured retinas. The additional stress in the form of dim light illumination for 8 h/day resulted in increased levels of the ER-stress markers GRP78/BiP and CHOP, as well as increased level of active caspase-12. Increased autophagic processes in cone and rod photoreceptors were detected by LC3B-II increases and occurrence of autophagosomes at the ultrastructural level. Illumination also resulted in altered protein expression for autophagy inducers such as p62 and Beclin-1. Moreover, there was a decrease in phosphorylated mammalian target of rapamycin (mTOR), which further indicate an increase of autophagy. Rod and cone photoreceptors in retinas from a diurnal animal that were exposed to dim light illumination in vitro displayed autophagy and ER-stress processes. As no alteration of rhodopsin mRNA was observed, autophagy and ER-stress are suggested to decrease rhodopsin protein at the posttranscriptional level. (C) 2014 Elsevier B.V. All rights reserved.

Keywords
Photoreceptor, Apoptosis, Autophagy, Endoplasmic reticulum stress, Porcine retina, Retinal degeneration
National Category
Ophthalmology
Research subject
Natural Science, Optometry
Identifiers
urn:nbn:se:lnu:diva-38485 (URN)10.1016/j.brainres.2014.08.055 (DOI)000343840300017 ()2-s2.0-84907653256 (Scopus ID)
Available from: 2014-12-03 Created: 2014-12-03 Last updated: 2017-12-05Bibliographically approved
Mohlin, C. & Johansson, K. (2011). Death of photoreceptors in organotypic retinal explant cultures: implication of rhodopsin accumulation and endoplasmic reticulum stress.. Journal of Neuroscience Methods, 197(1), 56-64
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
Mohlin, C., Liljekvist-Soltic, I. & Johansson, K. (2011). Further assessment of neuropathology in retinal explants and neuroprotection by human neural progenitor cells.. Journal of Neural Engineering, 8(6), Article ID: 066012
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
Mohlin, C., Liljekvist-Soltic, I., Olofsson, J. & Johansson, K. (2011). Neuropathology of cultured retinas: degenerative events and rescue paradigms. In: William L. Thomsen (Ed.), Advances in Eye Research. Volume 2: (pp. 177-190). Nova Science Publishers, Inc. (2)
Open this publication in new window or tab >>Neuropathology of cultured retinas: degenerative events and rescue paradigms
2011 (English)In: Advances in Eye Research. Volume 2 / [ed] William L. Thomsen, Nova Science Publishers, Inc., 2011, no 2, p. 177-190Chapter in book (Refereed)
Place, publisher, year, edition, pages
Nova Science Publishers, Inc., 2011
National Category
Ophthalmology
Research subject
Chemistry, Medical Chemistry
Identifiers
urn:nbn:se:lnu:diva-67989 (URN)978-1-61324-605-4 (ISBN)978-1-62257-129-1 (ISBN)
Available from: 2017-09-15 Created: 2017-09-15 Last updated: 2018-02-26Bibliographically approved
Gullberg, M., Tolf, C., Jonsson, N., Polacek, C., Precechtelova, J., Badurova, M., . . . Lindberg, A. M. (2010). A single coxsackievirus B2 capsid residue controls cytolysis and apoptosis in rhabdomyosarcoma cells.. Journal of Virology, 84(12), 5868-5879
Open this publication in new window or tab >>A single coxsackievirus B2 capsid residue controls cytolysis and apoptosis in rhabdomyosarcoma cells.
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2010 (English)In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 84, no 12, p. 5868-5879Article in journal (Refereed) Published
Abstract [en]

Coxsackievirus B2 (CVB2), one of six human pathogens of the group B coxsackieviruses within the enterovirus genus of Picornaviridae, causes a wide spectrum of human diseases ranging from mild upper respiratory illnesses to myocarditis and meningitis. The CVB2 prototype strain Ohio-1 (CVB2O) was originally isolated from a patient with summer grippe in the 1950s. Later on, CVB2O was adapted to cytolytic replication in rhabdomyosarcoma (RD) cells. Here, we present analyses of the correlation between the adaptive mutations of this RD variant and the cytolytic infection in RD cells. Using reverse genetics, we identified a single amino acid change within the exposed region of the VP1 protein (glutamine to lysine at position 164) as the determinant for the acquired cytolytic trait. Moreover, this cytolytic virus induced apoptosis, including caspase activation and DNA degradation, in RD cells. These findings contribute to our understanding of the host cell adaptation process of CVB2O and provide a valuable tool for further studies of virus-host interactions.

National Category
Microbiology in the medical area
Research subject
Biomedical Sciences, Virology
Identifiers
urn:nbn:se:lnu:diva-7168 (URN)10.1128/JVI.02383-09 (DOI)20375176 (PubMedID)2-s2.0-77952716030 (Scopus ID)
Available from: 2010-08-13 Created: 2010-08-13 Last updated: 2018-01-12Bibliographically approved
Englund-Johansson, U., Mohlin, C., Liljekvist-Soltic, I., Ekström, P. & Johansson, K. (2010). Human neural progenitor cells promote photoreceptor survival in retinal explants. Experimental Eye Research, 90(2), 292-299
Open this publication in new window or tab >>Human neural progenitor cells promote photoreceptor survival in retinal explants
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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
Liljekvist-Soltic, I., Olofsson, J. & Johansson, K. (2008). Progenitor cell-derived factors enhance photorecepto survival in rat retinal explants.. Brain Research, 1227, 226-233
Open this publication in new window or tab >>Progenitor cell-derived factors enhance photorecepto survival in rat retinal explants.
2008 (English)In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1227, p. 226-233Article in journal (Refereed) Published
Abstract [en]

Explantation of postnatal rat retinas is associated with degenerative events that show morphological similarities to human retinal degenerative disorders. The most evident morphological features are photoreceptor apoptosis involving caspase-3 and Müller cell activation. The purpose of the present study was to determine the content of protective factors in rat retinal progenitor cells and analyze the influence of the identified factors on the survival of photoreceptor cells and retinal gliosis. Tissue inhibitors of matrix metalloproteinase-1 (TIMP-1) and vascular endothelial growth factor (VEGF) were identified as putative beneficial factors, and their combined effect was examined in rat retinal explant cultures. Photoreceptor apoptosis was estimated by cell counts of cleaved caspase-3 and caspase-12 immunolabeled as well as TUNEL labeled cells. TIMP-1 and VEGF in combination significantly suppressed photoreceptor apoptosis involving caspase-3 activation. Cell counts of caspase-12 and TUNEL labeled photoreceptors showed no significant difference between the experiment and control retinas. TIMP-1 and VEGF appeared to have no effect on Müller cell activation as measured by GFAP and Ki-67 immunohistochemistry. Our data suggest that TIMP-1 and VEGF in combination promote the survival of photoreceptor cells in rat retinal explants, possibly by affecting a caspase-3 signaling pathway.

National Category
Natural Sciences
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-1815 (URN)10.1016/j.brainres.2008.06.077 (DOI)
Available from: 2010-04-06 Created: 2010-04-06 Last updated: 2017-12-12Bibliographically approved
Liljekvist-Larsson, I. & Johansson, K. (2007). Studies of host-graft interactions in vitro. Journal of Neural Engineering, 4, 255-263
Open this publication in new window or tab >>Studies of host-graft interactions in vitro
2007 (English)In: Journal of Neural Engineering, Vol. 4, p. 255-263Article in journal (Refereed) Published
National Category
Natural Sciences
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-1752 (URN)
Available from: 2010-04-06 Created: 2010-04-06 Last updated: 2011-10-13Bibliographically approved
Engelsberg, K., Johansson, K. & Ghosh, F. (2005). Culturing of porcine full-thickness retina.. Ophthalmic Research, 37, 104-111
Open this publication in new window or tab >>Culturing of porcine full-thickness retina.
2005 (English)In: Ophthalmic Research, Vol. 37, p. 104-111Article in journal (Refereed) Published
National Category
Medical and Health Sciences
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-1751 (URN)
Available from: 2010-04-06 Created: 2010-04-06 Last updated: 2011-09-30Bibliographically approved
Wasselius, J., Johansson, K., Håkansson, K., Abrahamson, M. & Ehinger, B. (2005). Cystatin C uptake in the eye.. Graefe´s Archive for Clinical and Experimental Ophthalmology, 243, 583-592
Open this publication in new window or tab >>Cystatin C uptake in the eye.
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2005 (English)In: Graefe´s Archive for Clinical and Experimental Ophthalmology, Vol. 243, p. 583-592Article in journal (Refereed) Published
National Category
Natural Sciences
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-1753 (URN)
Available from: 2010-04-06 Created: 2010-04-06 Last updated: 2011-09-30Bibliographically approved
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