A Method to Enhance Cell Survival on Bruch's Membrane in Eyes Affected by Age and Age-Related Macular Degeneration

Sugino, Ilene K.; Rapista, Aprille; Sun, Qian; Wang, Jianqiu; Nunes, Celia F.; Cheewatrakoolpong, Noounanong; Zarbin, Marco A.

doi:10.1167/iovs.11-8400

Cited by 37 publications

(33 citation statements)

References 35 publications

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“…Instead, transplanted cells were detectable in areas adjacent to areas of GA, where they were deposited onto native RPE. Organ culture experiments also underline that aged and thickened submacular human Bruch’s membrane (BM) does not support long-term survival and differentiation of transplanted RPE [107,108]. Thus, if RPE transplants are meant to preserve and rescue high-acuity vision, developing strategies to improve transplanted RPE cell survival in areas of GA, typically adjacent to the fovea, will be crucial.…”

Section: Cell-based Therapy In Amd: Current and Projected Clinicalmentioning

confidence: 99%

Tapping Stem Cells to Target AMD: Challenges and Prospects

Brandl

Graßmann

Riolfi

et al. 2015

JCM

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Human pluripotent stem cells (hPSCs) are increasingly gaining attention in biomedicine as valuable resources to establish patient-derived cell culture models of the cell type known to express the primary pathology. The idea of “a patient in a dish” aims at basic, but also clinical, applications with the promise to mimic individual genetic and metabolic complexities barely reflected in current invertebrate or vertebrate animal model systems. This may particularly be true for the inherited and complex diseases of the retina, as this tissue has anatomical and physiological aspects unique to the human eye. For example, the complex age-related macular degeneration (AMD), the leading cause of blindness in Western societies, can be attributed to a large number of genetic and individual factors with so far unclear modes of mutual interaction. Here, we review the current status and future prospects of utilizing hPSCs, specifically induced pluripotent stem cells (iPSCs), in basic and clinical AMD research, but also in assessing potential treatment options. We provide an outline of concepts for disease modelling and summarize ongoing and projected clinical trials for stem cell-based therapy in late-stage AMD.

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Section: Cell-based Therapy In Amd: Current and Projected Clinicalmentioning

confidence: 99%

Tapping Stem Cells to Target AMD: Challenges and Prospects

Brandl

Graßmann

Riolfi

et al. 2015

JCM

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“…At this time it is clear that, with certain precautions, stem cells can be produced en masse safely and that they can be induced to differentiate into ocular cells with the potential for replacement and rescue therapy. Challenges to successful stem cell therapy for degenerative retinal disease include the following: the abnormal microenvironment of the diseased eye, which can compromise cell survival and differentiation [103]; synaptic rewiring that accompanies retinal degeneration and which may compromise replacement strategies [104]; maintenance of functional phenotype over time; immune rejection, particularly for embryonic stem cell-derived RPE [105], and transplantation of ‘healthy' cells, particularly for induced pluripotent stem cell-derived RPE from AMD donors.…”

Section: Stem Cell Therapymentioning

confidence: 99%

Treatment of Dry Age-Related Macular Degeneration

et al. 2014

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A number of different approaches are under development for treating nonexudative manifestations of age-related macular degeneration (AMD). Some interventions target specific pathways that are believed to play a role in AMD pathogenesis, e.g. oxidative damage, lipofuscin accumulation, chronic inflammation (including complement activation), extracellular matrix changes (e.g. β-amyloid accumulation), impaired choroidal blood flow, and apoptosis. In principle, these therapies can be combined (‘combination therapy'), which may lead to synergistic effects that include better visual outcome, less likelihood for ‘escape' (i.e. drug resistance), and less frequent treatment.

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“…Nevertheless, in vitro, the alteration of the extracellular matrix (ECM) composition of Bruch's membrane through the addition of conditioned media helped the attachment of seeded RPE cells to aged Bruch's membrane. 126,[151][152][153] Another approach is to increase the surface levels of integrins. It has been shown that uncultured RPE cells from aged donors fail to adhere, s u r v i v e , o r f u n c t i o n o n B r u c h ' s m e mbrane.…”

Section: Enhancing the Adhesion And Survival Of Transplanted Rpe Cellsmentioning

confidence: 99%

Enhancing RPE Cell-Based Therapy Outcomes for AMD: The Role of Bruch's Membrane

Heller

Martin

2014

Trans. Vis. Sci. Tech.

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Age-related macular degeneration (AMD) is the leading cause of legal blindness in older people in the developed world. The disease involves damage to the part of the retina responsible for central vision. Degeneration of retinal pigment epithelial (RPE) cells, photoreceptors, and choriocapillaris may contribute to visual loss. Over the past decades, scientists and clinicians have tried to replace lost RPE cells in patients with AMD using cells from different sources. In recent years, advances in generating RPE cells from stem cells have been made and clinical trials are currently evaluating the safety and efficiency of replacing the degenerated RPE cell layer with stem cellderived RPE cells. However, the therapeutic success of transplantation of stem cellderived RPE cells may be limited unless the transplanted cells can adhere and survive in the long term in the diseased eye. One hallmark of AMD is the altered extracellular environment of Bruch's membrane to which the grafted cells have to adhere. Here, we discuss recent approaches to overcome the inhibitory environment of the diseased eye and to enhance the survival rate of transplanted RPE cells. Our aim is to highlight novel approaches that may have the potential to improve the efficacy of RPE transplantation for AMD in the future.

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A Method to Enhance Cell Survival on Bruch's Membrane in Eyes Affected by Age and Age-Related Macular Degeneration

Abstract: The results of this study indicate that RPE survival is possible on AMD BM and offer a method that could be developed for enhancing transplanted cell survival on AMD BM. Increased ECM deposition may account for improved cell survival after culture in BCEC-CM.

Cited by 37 publications

References 35 publications

Tapping Stem Cells to Target AMD: Challenges and Prospects

Tapping Stem Cells to Target AMD: Challenges and Prospects

Treatment of Dry Age-Related Macular Degeneration

Enhancing RPE Cell-Based Therapy Outcomes for AMD: The Role of Bruch's Membrane

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