Progranulin, a Major Secreted Protein of Mouse Adipose-Derived Stem Cells, Inhibits Light-Induced Retinal Degeneration

Tsuruma, Kazuhiro; Yamauchi, Mika; Sugitani, Sou; Otsuka, Tadashi; Ohno, Yuta; Nagahara, Yuki; Ikegame, Yuka; Shimazawa, Masamitsu; Yoshimura, Shinichi; Iwama, Toru; Hara, Hideaki

doi:10.5966/sctm.2013-0020

Cited by 47 publications

(48 citation statements)

References 40 publications

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“…If Progranulin and the lysosomal/proteolytic pathway could be upregulated, it is possible that excess lipopigment accumulation could be reversed in these patients prior to the degeneration of neurons. A recent study showed that Progranulin is a secreted factor of adipose-derived stem cells and shows protective effects against light-induced retinal damage in vivo (Tsuruma et al, 2013), suggesting that Progranulin may have neuroprotective properties.…”

Section: Discussionmentioning

confidence: 99%

Progressive retinal degeneration and accumulation of autofluorescent lipopigments in Progranulin deficient mice

et al. 2014

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Prior investigations have shown that patients with neuronal ceroid lipofuscinosis (NCL) develop neurodegeneration characterized by vision loss, motor dysfunction, seizures, and often early death. Neuropathological analysis of patients with NCL shows accumulation of intracellular autofluorescent storage material, lipopigment, throughout neurons in the central nervous system including in the retina. A recent study of a sibling pair with adult onset NCL and retinal degeneration showed linkage to the region of the progranulin (GRN) locus and a homozygous mutation was demonstrated in GRN. In particular, the sibling pair with a mutation in GRN developed retinal degeneration and optic atrophy. This locus for this form of adult onset neuronal ceroid lipofuscinosis was designated neuronal ceroid lipofuscinosis-11 (CLN11). Based on these clinical observations, we wished to determine whether Grn-null mice develop accumulation of autofluorescent particles and retinal degeneration. Retinas of both wild-type and Progranulin deficient mice were examined by immunostaining and autofluorescence. Accumulation of autofluorescent material was present in Progranulin deficient mice at 12 months. Degeneration of multiple classes of neurons including photoreceptors and retinal ganglion cells was noted in mice at 12 and 18 months. Our data shows that Grn −/− mice develop degenerative pathology similar to features of human CLN11.

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Section: Discussionmentioning

confidence: 99%

Progressive retinal degeneration and accumulation of autofluorescent lipopigments in Progranulin deficient mice

et al. 2014

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“…Another study identified a factor called progranulin as a major secreted protein of ADMSCs which showed protective effects against retinal damage both in vitro and in vivo. These findings suggest that ADMSCs have neuroprotective effects in the light-induced retinal damage model [26]. …”

Section: Discussionmentioning

confidence: 99%

Subretinal adipose tissue-derived mesenchymal stem cell implantation in advanced stage retinitis pigmentosa: a phase I clinical safety study

et al. 2016

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BackgroundThis prospective clinical case series aimed to investigate the safety of subretinal adipose tissue-derived mesenchymal stem cell (ADMSC) implantation in advanced stage retinitis pigmentosa (RP).MethodsThis study included 11 patients with end-stage RP who received subretinal implantation of ADMSCs. All patients had a total visual field defect and five of them only had light perception. The best corrected visual acuity (BCVA) in the study was 20/2000. All patients had undetectable electroretinography (ERG). The worst eye of the patient was operated on and, after total vitrectomy with a 23 gauge, ADMSCs were injected subretinally. Patients were evaluated at day 1, at weeks 1–4, and then once a month for 6 months, postoperatively. BCVA, anterior segment and fundus examination, color photography, and optical coherence tomography (OCT) were carried out at each visit. Fundus fluorescein angiography (FFA), perimetry, and ERG recordings were performed before treatment and at the end of month 6, and anytime if necessary during the follow-up.ResultsAll 11 patients completed the 6-month follow-up. None of them had systemic complications. Five patients had no ocular complications. One of the patients experienced choroidal neovascular membrane (CNM) at the implantation site and received an intravitreal anti-vascular endothelial growth factor drug once. Five patients had epiretinal membrane around the transplantation area and at the periphery, and received a second vitrectomy and silicon oil injection. There was no statistically significant difference in BCVA and ERG recordings from baseline. Only one patient experienced an improvement in visual acuity (from 20/2000 to 20/200), visual field, and ERG. Three patients mentioned that the light and some colors were brighter than before and there was a slight improvement in BCVA. The remaining seven patients had no BCVA improvement (five of them only had light perception before surgery).ConclusionsStem cell treatment with subretinal implantation of ADMSCs seems to have some ocular complications and should be applied with caution. The results of this study provide the first evidence of the short-term safety of ADMSCs in humans, and clarifies the complications of the therapy which would be beneficial for future studies. To optimize the cell delivery technique and to evaluate the effects of this therapy on visual acuity and the quality of life of these patients, future studies with a larger number of cases will be necessary.

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“…ASCs express a number of biological proteins involved in the promotion of cell viability, including transforming growth factor β 1 (27,33) and progranulin (34). However, numerous studies have demonstrated the anti-proliferative or anti-tumorigenic effects of ASCs.…”

Section: Ink4amentioning

confidence: 99%

“…ASCs produce various growth factors and adipokines, thus, the cells function as an endocrine or paracrine organ that is considered to perform a pivotal role in maintaining a suitable microenvironment for the regulation of tumor initiation, progression and metastasis (27,(33)(34)(35). ASCs express a number of biological proteins involved in the promotion of cell viability, including transforming growth factor β 1 (27,33) and progranulin (34).…”

Section: Ink4amentioning

confidence: 99%

Effect of adipose-derived stem cell-conditioned medium on the proliferation and migration of B16 melanoma cells

et al. 2015

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Progranulin, a Major Secreted Protein of Mouse Adipose-Derived Stem Cells, Inhibits Light-Induced Retinal Degeneration

Cited by 47 publications

References 40 publications

Progressive retinal degeneration and accumulation of autofluorescent lipopigments in Progranulin deficient mice

Progressive retinal degeneration and accumulation of autofluorescent lipopigments in Progranulin deficient mice

Subretinal adipose tissue-derived mesenchymal stem cell implantation in advanced stage retinitis pigmentosa: a phase I clinical safety study

Effect of adipose-derived stem cell-conditioned medium on the proliferation and migration of B16 melanoma cells

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