Human neural progenitor cells promote photoreceptor survival in retinal explants

Englund-Johansson, Ulrica; Mohlin, Camilla; Liljekvist-Soltic, Ingela; Ekström, Per; Johansson, Kjell

doi:10.1016/j.exer.2009.11.005

Cited by 25 publications

(27 citation statements)

References 48 publications

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“…As shown by the present results, apoptotic signals can be detected in PD12 retinal explants. This is in line with previous findings demonstrating active cell death in rodent retinal explants (Englund-Johansson et al 2010;Guerin et al 2011;McKernan et al 2006). The fact that levels of apoptotic signals differ between WT and KO retinas suggests that cell death can be regulated by sst 2 expression in the retina.…”

Section: Apoptotic Signals and Octreotide Effectssupporting

confidence: 89%

Protective role of somatostatin receptor 2 against retinal degeneration in response to hypoxia

Monte

Latina

Cupisti

et al. 2012

Naunyn-Schmiedeberg's Arch Pharmacol

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In mouse retinal explants, octreotide, a somatostatin [somatotropin release-inhibiting factor (SRIF)] receptor 2 (sst(2)) agonist, prevents the hypoxia-induced vascular endothelial growth factor upregulation. In mice with oxygen-induced retinopathy (OIR), a model of retinopathy of prematurity, either sst(2) overexpression or octreotide have been found to limit hypoxia-induced angiogenic processes. Here, we investigated whether sst(2) influences retinal degeneration in response to hypoxia in wild-type (WT), sst(1)- and sst(2)-knockout (KO) mice. In retinal explants, we determined the role of sst(2) on apoptotic signals. In control condition, caspase-3 activity and the Bax/Bcl-2 ratio were lower in sst(1)-KO than in WT, but higher in sst(2)-KO than in WT retinas. In all strains, a comparable increase in caspase-3 activity and the Bax/Bcl-2 ratio was observed after hypoxia. The hypoxia-induced increase in apoptotic signals was recovered by octreotide in both WT and sst(1)-KO retinas. To investigate the role of sst(2) on retinal function, we recorded electroretinogram (ERG) in response to light flashes in OIR mice. ERG responses did not differ between WT and KO mice with the exception of oscillatory potentials (OPs) which, in sst(1)-KO mice, displayed much larger amplitude. In all strains, hypoxia drastically reduced a-, b-waves and OPs. In both WT and sst(1)-KO mice, octreotide recovered a- and b-waves, but did not recover OPs in sst(1)-KO mice. Neither apoptotic signals nor ERG was affected by octreotide in sst(2)-KO mice. These results show that sst(2) may protect retinal cells from hypoxia, thus implementing the background to establish potential pharmacological targets based on sst(2) pharmacology.

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Section: Apoptotic Signals and Octreotide Effectssupporting

confidence: 89%

Protective role of somatostatin receptor 2 against retinal degeneration in response to hypoxia

Monte

Latina

Cupisti

et al. 2012

Naunyn-Schmiedeberg's Arch Pharmacol

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“…Compared to stem cells, progenitor cells have the benefit of reduced proliferative capacity, and consequently no tumor formation has been seen after extensive use of hNPC ctx in various animal models. [23][24][25][26]28 Ki67 (a proliferation marker) was expressed at only low numbers in the nestin-positive human progenitor cells (Fig. 4F), confirming that the majority of hNPC ctx ceases to proliferate following retinal transplantation.…”

Section: Hnpc Transplant Survival Distribution and Phenotypementioning

confidence: 56%

“…Finally, hNPC ctx do not compromise normal retinal function after subretinal transplantation into nonhuman primates 22 and do not appear to form tumors following transplantation in the central nervous system (CNS). [23][24][25][26][27][28] While there are several clinical trials using stem/ progenitor cells to treat retinal degeneration (ClinicalTrials.gov), some fundamental questions remain to be addressed. Stem cells are among the most complex biological therapeutic entities proposed for clinical use.…”

Section: Introductionmentioning

confidence: 99%

A Subsequent Human Neural Progenitor Transplant into the Degenerate Retina Does Not Compromise Initial Graft Survival or Therapeutic Efficacy

Lü

Lin

Tsai

et al. 2015

Trans. Vis. Sci. Tech.

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“…Caspase-3-mediated photoreceptor degenerations have been observed previously in cultured rodent retinas (Mohlin and Johansson, 2011;Englund-Johansson et al, 2010), which possess a rod-dominated retina with a small subpopulation of cones. Although insignificant, we also observed increased protein levels of cleaved caspase-3 in homogenates of illuminated cultured specimens.…”

Section: Opsin Accumulation and Cyclic Illumination Promote Er-stressmentioning

confidence: 56%

Autophagy and ER-stress contribute to photoreceptor degeneration in cultured adult porcine retina

et al. 2014

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Abbreviations: AMD, age-related macular degeneration; BSA, bovine serum albumin; CHOP, C/EBP homology protein; CtBP2, C-terminal binding protein 2; ER, endoplasmic reticulum; GRP78/BiP, glucoseregulated protein 78kDa/Binding immunoglobulin protein, INL, inner nuclear layer; IPL, inner plexiform layer; LC3B, microtubule-associated protein light chain 3B; mTOR, mammalian target of rapamycin; ONL, outer nuclear layer; OPL, outer nuclear layer; PBS, phosphate buffered saline; PNA, peanut agglutinin; p62/SQSTM1; nucleoporin p62/sequestosom 1; PSD-95, postsynaptic density protein 95; rd1, retinal degeneration 1; RPE, retinal pigment epithelium; UPS, ubiquitin-proteasome system; 2 AbstractThe 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 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. In particular, these processes resulted in decreased protein levels for rhodopsin.3

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Human neural progenitor cells promote photoreceptor survival in retinal explants

Cited by 25 publications

References 48 publications

Protective role of somatostatin receptor 2 against retinal degeneration in response to hypoxia

Protective role of somatostatin receptor 2 against retinal degeneration in response to hypoxia

A Subsequent Human Neural Progenitor Transplant into the Degenerate Retina Does Not Compromise Initial Graft Survival or Therapeutic Efficacy

Autophagy and ER-stress contribute to photoreceptor degeneration in cultured adult porcine retina

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