![]() Most bestrophinopathy patients will maintain robust central vision well into the fifth decade of life, 15 as cones can tolerate subretinal fluid for many years. While bestrophinopathies progressively worsen with age, the rate of decline is typically slow and provides a long therapeutic window, as central photoreceptors remain viable for decades despite the persistence of subretinal fluid and serous detachment ( Figures 2 and ​ 3 3). FA is absent in the central area, which exhibits dystrophic RPE and loss of photoreceptors. Photoreceptor mitochondrial band has disintegrated at various points, indicated by black arrows. Severe phenotypic manifestation in a 42-year-old VMD patient with p. Severe vitelliform macular degeneration (VMD). Experimentally, eyes provide the ideal treatment-control groups, as the contralateral, untreated eye can be compared with the intervention eye. The blood–retina barrier provides relative immune privilege, and in the event of teratoma formation, the eye can be removed without risk of damaging other organ systems and is itself not a life-threatening event. ![]() In fact, the eye is one of the only organs that permits remarkably targeted interventions that are not highly invasive or systemic. ![]() The ability to quantify efficacy in subjects in a noninvasive manner at multiple time points is a major advantage of conducting research on the eye, one shared by few if any other organ systems. Numerous noninvasive techniques such as fundus autofluorescence, optical coherence tomography (OCT), and adaptive optics imaging enable micron-level examination of the inside of the retina in live animals and patients. The human retina is the ideal testing ground for assessing experimental gene and cell therapies because of its relative immune privilege and accessibility for monitoring, imaging, and surgical manipulation. Several of these debilitating blinding disorders have recently become targets for gene 3, 4, 5, 6, 7 and cell 8 therapies. 1 Aside from cancer, blindness is one of the most feared medical conditions among Americans, 2 and for many patients, the diagnosis of an eye disease implies reduced independence and limited ability to conduct normal, day-to-day activities. RPE disorders, including bestrophinopathy, some forms of retinitis pigmentosa, and age-related macular degeneration, affect more than 10 million Americans, an incidence that is expected to double by 2020 and will place a significant burden on public health. The Eye: An Ideal Environment for Experimental Gene and Cell-Based Therapies This mini-review will briefly highlight the suitability of the retina for gene and cell therapies, the pathophysiology of bestrophinopathy, and the research and treatment opportunities afforded by stem cell and genetic therapies. Recent studies on induced pluripotent stem (iPS)-RPE generation indicate strong potential for developing patient-specific disease models in vitro, which could eventually enable personalized treatment. The year 2011 brought a new advance in cell-based therapies, with the Food and Drug Administration approving clinical trials using embryonic stem cells for an RPE disorder known as age-related macular degeneration. Several RPE disorders have recently become targets for gene therapies in humans. RPE disorders and allied retinal degenerations exhibit significant genetic heterogeneity, and diverse mutations can result in similar disease phenotypes. A retinal pigmented epithelial (RPE) disorder, bestrophinopathy has recently been proven to be amenable to gene and cell-based therapies in preclinical models.
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