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BACKGROUND: The World Health Organization (WHO) estimates that the number of individuals who lose their vision due to retinal degeneration is expected to reach 6 million annually in 2020. The retinal degenerative diseases affect the macula, which is responsible for central and detailed vision. Most macular degeneration, i.e., age-related macular degeneration (AMD) develops in the elderly; however, certain hereditary diseases, such as the Stargardt disease, also affect young people. This degeneration begins with loss of retinal pigmented epithelium (RPE) due to formation of drusen (atrophic) or abnormal vessels (exudative). In wet AMD, numerous drugs are available to successful treat the disease; however, no proven therapy currently is available to treat dry AMD or Stargardt. Since its discovery, human embryonic stem cells (hESCs) have been considered a valuable therapeutic tool. Some evidence has shown that transplantation of RPEs differentiated from hESCs cells can result in recovery of both RPE and photoreceptors and prevent visual loss. METHODS: The human embryonic WA-09 stem cell lineage was cultured under current Good Manufacturing Practices (cGMP) conditions using serum-free media and supplements. The colonies were isolated manually and allowed to spontaneously differentiate into RPE cells. RESULTS: This simple and effective protocol required minimal manipulation and yielded more than 10e8 RPE cells by the end of the differentiation and enrichment processes, with cells exhibiting a cobblestone morphology and displaying cellular markers and a gene expression profile typical of mature RPE cells. Moreover, the differentiated cells displayed phagocytic activity and only a small percentage of the total cells remained positive for the Octamer-binding transcriptions factor 4 (OCT-4) pluripotency cell marker. CONCLUSIONS: These results showed that functional RPE cells can be produced efficiently and suggested the possibility of scaling-up to aim at therapeutic protocols for retinal diseases associated with RPE degeneration.
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BACKGROUND: Subretinal cell transplantation is a challenging surgical maneuver. This paper describes the preliminary findings of a new tissue injector for subretinal implantation of an ultrathin non-absorbable substrate seeded with human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE). METHODS: Ultrathin Parylene-C substrates measuring 3.5 mm × 6.0 mm seeded with hESC-RPE (implant referred to as CPCB-RPE1) were implanted into the subretinal space of 12 Yucatan minipigs. Animals were euthanized immediately after the procedure and underwent spectral domain optical coherence tomography (SD-OCT) and histological analysis to assess the subretinal placement of the implant. Evaluation of the hESC-RPE cells seeded on the substrate was carried out before and after implantation using standard cell counting techniques. RESULTS: The tissue injector delivered the CPCB-RPE1 implant through a 1.5 mm sclerotomy and a 1.0-1.5 mm retinectomy. SD-OCT scans and histological examination revealed that substrates were precisely placed in the subretinal space, and that the hESC-RPE cell monolayer continued to cover the surface of the substrate after the surgical procedure. CONCLUSION: This innovative tissue injector was able to efficiently deliver the implant in the subretinal space of Yucatan minipigs, preventing significant hESC-RPE cell loss, minimizing tissue trauma, surgical complications and postoperative inflammation.
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INTRODUCTION: The term visual prosthesis refers to any device capable of eliciting visual percepts in an individual through electrical stimulation of any part of the visual system. BACKGROUND: Blindness can be due to eye pathology or due to damage of the lateral geniculate or visual cortex. Eye pathology other than diseases that affect the cornea and lens are numerous and some of the leading causes are diabetic retinopathy, age-related macular degeneration, retinal detachment, glaucoma, and retinal vascular occlusions. The visual prosthesis can be divided into non-retinal and retinal approaches. Non-retinal approaches include cortical and optic nerve prosthesis. Retinal approaches are aimed at eye pathologies in which at least part of the optic nerve remains intact whereas when the optic nerve is nearly completely damaged and/or the eye itself is disfigured or degenerated then a non-retinal approach is warranted. The retinal prosthesis can be placed on the surface of the retina, in the subretinal space or in the suprachoroidal space. RESULTS: Several independent groups related variable degrees of success in promoting visual sensations through electrical stimulation of the visual system. Every technique, equipment and anatomical target has its advantages and disadvantages, and the biological/electrical-mechanical interface is still the aspect of the research towards a chronic, long term, reliable biomimetic implant. CONCLUSIONS: The visual prostheses have achieved significant developments in recent years. We see continued improvement in visual acuity with increasing number and density of electrodes. Even though the visual acuity is still poor relative to normal vision, these subjects can read letters using their implants. Perhaps more importantly, blind patients can use these devices for mobility and orientation.