Stemming vision loss with stem cells

Marchetti, Valentina; Krohne, Tim U.; Friedlander, David F.; Friedlander, Martin

doi:10.1172/jci42951

Cited by 41 publications

(40 citation statements)

References 119 publications

(131 reference statements)

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“…Injection of BMSCs into the eye improves retinal circulation, enhances survival of outer retinal neurons, and rescues vision in both ischemic and nonischemic mouse models of retinal degeneration [53,55]. These findings open a new paradigm for the relationship between vasculature and the neural retina in which neurotrophic effects secondary to improved circulation after BMSC transplantation benefits both ischemic and nonischemic retinal degenerations [56,57].…”

Section: Non-neural Stem Cellsmentioning

confidence: 80%

Stem Cells for Retinal Replacement Therapy

Stern

Temple

2011

Neurotherapeutics

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Retinal degenerative disease has limited therapeutic options and the possibility of stem cell-mediated regenerative treatments is being actively explored for these blinding retinal conditions. The relative accessibility of this central nervous system tissue and the ability to visually monitor changes after transplantation make the retina and adjacent retinal pigment epithelium prime targets for pioneering stem cell therapeutics. Prior work conducted for several decades indicated the promise of cell transplantation for retinal disease, and new strategies that combine these established surgical approaches with stem cell-derived donor cells is ongoing. A variety of tissue-specific and pluripotent-derived donor cells are being advanced to replace lost or damaged retinal cells and/or to slow the disease processes by providing neuroprotective factors, with the ultimate aim of long-term improvement in visual function. Clinical trials are in the early stages, and data on safety and efficacy are widely anticipated. Positive outcomes from these stem cell-based clinical studies would radically change the way that blinding disorders are approached in the clinic.

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Section: Non-neural Stem Cellsmentioning

confidence: 80%

Stem Cells for Retinal Replacement Therapy

Stern

Temple

2011

Neurotherapeutics

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“…Cell-based therapies, with tion to uniformly cover the entire tissue suboptimal. For example, in age-related macular degeneration, cell thertheir tissue regeneration potential (20,24) and paracrine effects (either innate or through genetic modification) apy needs to be directed specifically at the macular region of the retina since cells delivered into the periph- (18,19,23,46), have many advantages over other treatment modalities. As such cell therapies move towards eral retina will have no functional benefit or might even disrupt normal tissue function.…”

Section: Introductionmentioning

confidence: 99%

Focused Magnetic Stem Cell Targeting to the Retina Using Superparamagnetic Iron Oxide Nanoparticles

et al. 2012

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Developing new ways of delivering cells to diseased tissue will be a key factor in translating cell therapeutics research into clinical use. Magnetically targeting cells enables delivery of significant numbers of cells to key areas of specific organs. To demonstrate feasibility in neurological tissue, we targeted cells magnetically to the upper hemisphere of the rodent retina. Rat mesenchymal stem cells (MSCs) were magnetized using superparamagnetic iron oxide nanoparticles (SPIONs). In vitro studies suggested that magnetization with fluidMAG-D was well tolerated, that cells remained viable, and they retained their differentiation capabilities. FluidMAG-D-labeled MSCs were injected intravitreally or via the tail vein of the S334ter-4 transgenic rat model of retinal degeneration with or without placing a gold-plated neodymium disc magnet within the orbit, but outside the eye. Retinal flatmount and cryosection imaging demonstrated that after intravitreal injection cells localized to the inner retina in a tightly confined area corresponding to the position of the orbital magnet. After intravenous injection, similar retinal localization was achieved and remarkably was associated with a tenfold increase in magnetic MSC delivery to the retina. Cryosections demonstrated that cells had migrated into both the inner and outer retina. Magnetic MSC treatment with orbital magnet also resulted in significantly higher retinal concentrations of anti-inflammatory molecules interleukin-10 and hepatocyte growth factor. This suggested that intravenous MSC therapy also resulted in significant therapeutic benefit in the dystrophic retina. With minimal risk of collateral damage, these results suggest that magnetic cell delivery is the best approach for controlled delivery of cells to the outer retina-the focus for disease in age-related macular degeneration and retinitis pigmentosa.

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“…93 Various poorly monitored ‘stem cell institutes' worldwide are promoting the use of non-validated experimental protocols, and patients with LHON and DOA need to be carefully advised before embarking on multiple expensive courses of treatment with the possible associated biological risks. In sharp contrast to this unregulated parallel market, there are a number of well-established research programmes that are rigorously assessing the possible application of stem cell technology for optic nerve disorders.…”

Section: Future Prospects and Challengesmentioning

confidence: 99%

Treatment strategies for inherited optic neuropathies: past, present and future

Yu‐Wai‐Man

Votruba

Moore

et al. 2014

Eye

128

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Bilateral visual loss secondary to inherited optic neuropathies is an important cause of registrable blindness among children and young adults. The two prototypal disorders seen in clinical practice are Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (DOA). About 90% of LHON cases are due to one of three mitochondrial DNA (mtDNA) point mutations: m.3460G>A, m.11778G>A, and m.14484T>C, which affect critical complex I subunits of the mitochondrial respiratory chain. The majority of patients with DOA harbour pathogenic mutations within OPA1, a nuclear gene that codes for a multifunctional inner mitochondrial membrane protein. Despite their contrasting genetic basis, LHON and DOA share overlapping pathological and clinical features that serve to highlight the striking tissue-specific vulnerability of the retinal ganglion cell (RGC) layer to disturbed mitochondrial function. In addition to severe visual loss secondary to progressive optic nerve degeneration, a subgroup of patients will also develop a more aggressive syndromic phenotype marked by significant neurological deficits. The management of LHON and DOA remains largely supportive, but major advances in our understanding of the mechanisms underpinning RGC loss in these two disorders are paving the way for novel forms of treatment aimed at halting or reversing visual deterioration at different stages of the disease process. In addition to neuroprotective strategies for rescuing RGCs from irreversible cell death, innovative in vitro fertilisation techniques are providing the tantalising prospect of preventing the germline transmission of pathogenic mtDNA mutations, eradicating in so doing the risk of disease in future generations.

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Stemming vision loss with stem cells

Cited by 41 publications

References 119 publications

Stem Cells for Retinal Replacement Therapy

Stem Cells for Retinal Replacement Therapy

Focused Magnetic Stem Cell Targeting to the Retina Using Superparamagnetic Iron Oxide Nanoparticles

Treatment strategies for inherited optic neuropathies: past, present and future

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