Subretinal transplantation of genetically modified human cell lines attenuates loss of visual function in dystrophic rats

Lund, Raymond D.; Adamson, Peter; Sauvé, Yves; Keegan, David; Girman, Sergey; Wang, Shaomei; Winton, Helen L; Kanuga, Naheed; Kwan, Anthony; Beauchéne, Laurence; Zerbib, A; Hetherington, L; Couraud, Pierre‐Olivier; Coffey, Peter; Greenwood, John

doi:10.1073/pnas.171266298

Cited by 179 publications

(126 citation statements)

References 25 publications

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“…13,14 In the behavior tests of this study, we demonstrated that the RCS rats with the dye-coupled film implantation restored the vision in the course of 8 weeks of the observation after the surgery at the age of 6 weeks, compared with the rats with the plain film implantation. In this study, two movements of rats were observed in the behavior tests: head-turning and body-turning in the direction, consistent with the clockwise and anticlockwise rotation of the black-and-white-striped drum.…”

Section: Discussionmentioning

confidence: 56%

“…This finding was consistent with previous studies on the behavior tests which utilized the number of head-turning as a sole indicator. 13,14 The speed of the rotation of the black-and-white-striped drum was set at 2 rpm or 4 rpm, based on the previous reports. 13,14 The present results suggest that the slower speed at 2 rpm would be better, than the faster speed at 4 rpm, for assessing the rats' vision.…”

Section: Discussionmentioning

confidence: 99%

“…A drum at the diameter of 40 cm, with the inside painted with black-and-white stripes, was rotated around the cage at the speed of 2 or 4 rounds per minute (rpm). 13,14 Each black or white stripe on the drum had the width of 5 degrees, and the drum contained 36 black stripes and 36 white stripes in the entire 360-degree circumference. The behavior of rats was recorded by a digital videocamera 9 from above ( Fig.…”

Section: Behavior Testmentioning

confidence: 99%

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Behavior tests and immunohistochemical retinal response analyses in RCS rats with subretinal implantation of Okayama-University-type retinal prosthesis

et al. 2013

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We have developed a photoelectric dye-coupled polyethylene film as a prototype of retinal prosthesis, named "Okayama University-type retinal prosthesis. The purposes of this study are to conduct behavior tests to assess vision in Royal College of Surgeons (RCS) rats which underwent subretinal implantation of the dye-coupled film, and are also to reveal the retinal response to the dye-coupled film by immunohistochemistry.Polyethylene films were made of polyethylene powder at refined purity, and photoelectric dyes were coupled to the film surface at higher density, compared with the prototype. The dye-coupled film or the dye-uncoupled plain film, as a control, was implanted subretinally from a scleral incision in both eyes of a RCS rat at 6 weeks of the age. Behavior tests, 2, 4, 6, and 8 weeks after the implantation, were conducted by observing head-turning or body-turning in the direction, consistent with clockwise or anticlockwise rotation of a black-and-white-striped drum around a transparent cage, housed with a rat. After the behavior tests at 8 weeks, rats' eyes were enucleated to confirm the subretinal implantation of the films and were processed for immunohistochemistry. In the behavior tests, the number of head-turning, consistent with the direction of the drum rotation, was significantly larger in RCS rats with dye-coupled film implantation, compared with rats with plain film implantation (P<0.05, 3 repeated-measure ANOVA). The number of apoptotic neurons was significantly smaller in the eyes with the dye-coupled film implantation, compared to the eyes with the plain film (P<0.05, Mann-Whitney U-test). In conclusion, subretinal implantation of the photoelectric dye-coupled films restored the vision in RCS rats and prevented the remaining retinal neurons from apoptosis.

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Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Behavior Testmentioning

confidence: 99%

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Behavior tests and immunohistochemical retinal response analyses in RCS rats with subretinal implantation of Okayama-University-type retinal prosthesis

et al. 2013

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“…They also phagocytose apically presented ROS, albeit with slower kinetics and without circadian regulation (Campochiaro et al 1991;Dunn et al 1996;Tian et al 2004;Turowski et al 2004). In addition, subretinal transplantation of ARPE-19 cells into developing dystrophic rat retinas, which are genetically impaired in RPE function, has been shown to rescue RPE function (Lund et al 2001). Therefore, ARPE-19 cells retain the capacity to become fully functioning RPE and are a good model for the study of the certain aspects of RPE biology.…”

Section: Introductionmentioning

confidence: 99%

The unconventional myosin-VIIa associates with lysosomes

Soni

Warren

Bucci

et al. 2005

Cell Motil. Cytoskeleton

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Mutations in the myosin-VIIa (MYO7a) gene cause human Usher disease, characterized by hearing impairment and progressive retinal degeneration. In the retina, myosin-VIIa is highly expressed in the retinal pigment epithelium, where it plays a role in the positioning of melanosomes and other digestion organelles. Using a human cultured retinal pigmented epithelia cell line, ARPE-19, as a model system, we have found that a population of myosin-VIIa is associated with cathepsin D-and Rab7-positive lysosomes. Association of myosin-VIIa with lysosomes was Rab7 independent, as dominant negative and dominant active versions of Rab7 did not disrupt myosin-VIIa recruitment to lysosomes. Association of myosin-VIIa with lysosomes was also independent of the actin and microtubule cytoskeleton. Myosin-VIIa copurified with lysosomes on density gradients, and fractionation and extraction experiments suggested that it was tightly associated with the lysosome surface. These studies suggest that myosin-VIIa is a lysosome motor.

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“…RPE cell transformations can occur spontaneously, such as with the ARPE19 and the D407 cell lines, 56,57 but may also be genetically engineered for example, H1RPE7. 58 RPE cells can also be genetically modified to alter some other aspect of their behaviour, so that they either express a marker (eg. Green Fluorescent Protein (GFP)-labelled RPE) or modify gene expression.…”

Section: Eyementioning

confidence: 99%

Retinal pigment epithelium transplantation: concepts, challenges, and future prospects

Alexander

Thomson

Luff

et al. 2015

Eye

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The retinal pigment epithelium (RPE) is a single layer of cells that supports the light-sensitive photoreceptor cells that are essential for retinal function. Age-related macular degeneration (AMD) is a leading cause of visual impairment, and the primary pathogenic mechanism is thought to arise in the RPE layer. RPE cell structure and function are well understood, the cells are readily sustainable in laboratory culture and, unlike other cell types within the retina, RPE cells do not require synaptic connections to perform their role. These factors, together with the relative ease of outer retinal imaging, make RPE cells an attractive target for cell transplantation compared with other cell types in the retina or central nervous system. Seminal experiments in rats with an inherited RPE dystrophy have demonstrated that RPE transplantation can prevent photoreceptor loss and maintain visual function. This review provides an update on the progress made so far on RPE transplantation in human eyes, outlines potential sources of donor cells, and describes the technical and surgical challenges faced by the transplanting surgeon. Recent advances in the understanding of pluripotent stem cells, combined with novel surgical instrumentation, hold considerable promise, and support the concept of RPE transplantation as a regenerative strategy in AMD.

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Subretinal transplantation of genetically modified human cell lines attenuates loss of visual function in dystrophic rats

Cited by 179 publications

References 25 publications

Behavior tests and immunohistochemical retinal response analyses in RCS rats with subretinal implantation of Okayama-University-type retinal prosthesis

Behavior tests and immunohistochemical retinal response analyses in RCS rats with subretinal implantation of Okayama-University-type retinal prosthesis

The unconventional myosin-VIIa associates with lysosomes

Retinal pigment epithelium transplantation: concepts, challenges, and future prospects

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