Induced pluripotent stem cell therapies for geographic atrophy of age-related macular degeneration.

Institute for Genomic Medicine and Shiley Eye Center, University of California at San Diego, La Jolla, CA 92093, USA.
Seminars in ophthalmology (Impact Factor: 1.2). 05/2011; 26(3):216-24. DOI: 10.3109/08820538.2011.577498
Source: PubMed

ABSTRACT There is currently no FDA-approved therapy for treating patients with geographic atrophy (GA), a late stage of age-related macular degeneration (AMD). Cell transplantation has the potential to restore vision in these patients. This review discusses how recent advancement in induced pluripotent stem (iPS) cells provides a promising therapy for GA treatment. Recent advances in stem cell biology have demonstrated that it is possible to derive iPS cells from human somatic cells by introducing reprogramming factors. Human retinal pigment epithelium (RPE) cells and photoreceptors can be derived from iPS cells by defined factors. Studies show that transplanting these cells can stabilize or recover vision in animal models. However, cell derivation protocols and transplantation procedures still need to be optimized. Much validation has to be done before clinical-grade, patient-derived iPS can be applied for human therapy. For now, RPE cells and photoreceptors derived from patient-specific iPS cells can serve as a valuable tool in elucidating the mechanism of pathogenesis and drug discovery for GA.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Age-related macular degeneration (AMD) is a degenerative disease of the eye that has been a subject of numerous studies in pathogenesis as well as clinical research in treatment owing to its notoriety as the leading cause of irreversible blindness in the elderly. Genetic studies have elucidated various pathways related to inflammation that contribute to AMD development such as those of the complement system, coagulation system, and the immune system. The current standard of treatment in AMD is inhibition of neovascularization using anti-vascular endothelial growth factor antibodies, which is effective in wet AMD. Furthermore, the absence of screening methods or preventive measures for AMD poses yet another challenge. Stem cell therapy now holds great promise for various diseases, and AMD may well be one of the earliest diseases such treatment modality may be employed, considering the unique characteristics of the eye as a localized and immune-privileged organ.
    Fetal ovine model for in-situ esophagus tissue engineering 08/2013; 10(4):164-175. DOI:10.1007/s13770-012-0374-0 · 0.61 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Currently, there is no treatment to stop the progression of geographic atrophy, the advanced form of non-exudative (dry) age-related macular degeneration. Several promising therapies are being investigated in clinical trials such as antioxidants, neuroprotection agents, complement inhibitors, vascular enhancers, visual cycle modulators, and stem cell therapies. This review discusses the possible treatments that may potentially be available in the future to prevent disease progression.
    03/2014; 2(1):20-25. DOI:10.1007/s40135-013-0036-y
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    Journal of Clinical Medicine Research 02/2015; 4(2015 4):282-303. DOI:10.3390/jcm4020282