Retinal Pigment Epithelium and Photoreceptor Transplantation Frontiers

Gullapalli, Vamsi K.; Khodair, Mohamad A.; Wang, Hao; Sugino, Ilene K.; Madreperla, Steven A.; Zarbin, Marco A.

doi:10.1016/b978-0-323-02598-0.50159-2

Cited by 11 publications

(8 citation statements)

References 268 publications

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“…However, numerous problems continue to plague clinical translation, including the risk of teratoma formation and the need for powerful drugs to overcome the problem of immune rejection. Until somatic cell nuclear transfer or induced pluripotent stem cell technology is further developed, diseases affecting the eye—a relative immunoprivileged site [2]—are likely to be among the first hESC‐derived therapies. In the retina, compromised retinal pigment epithelial cell (RPE) function can lead to deteriorated vision and photoreceptor loss in both age‐related macular degeneration and some forms of retinitis pigmentosa [3–7].…”

Section: Introductionmentioning

confidence: 99%

Long-Term Safety and Function of RPE from Human Embryonic Stem Cells in Preclinical Models of Macular Degeneration

et al. 2009

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Assessments of safety and efficacy are crucial before human ESC (hESC) therapies can move into the clinic. Two important early potential hESC applications are the use of retinal pigment epithelium (RPE) for the treatment of age-related macular degeneration and Stargardt disease, an untreatable form of macular dystrophy that leads to early-onset blindness. Here we show long-term functional rescue using hESC-derived RPE in both the RCS rat and Elov14 mouse, which are animal models of retinal degeneration and Stargardt, respectively. Good Manufacturing Practice-compliant hESC-RPE survived subretinal transplantation in RCS rats for prolonged periods (>220 days). The cells sustained visual function and photoreceptor integrity in a dose-dependent fashion without teratoma formation or untoward pathological reactions. Near-normal functional measurements were recorded at >60 days survival in RCS rats. To further address safety concerns, a Good Laboratory Practice-compliant study was carried out in the NIH III immune-deficient mouse model. Long-term data (spanning the life of the animals) showed no gross or microscopic evidence of teratoma/ tumor formation after subretinal hESC-RPE transplantation. These results suggest that hESCs could serve as a potentially safe and inexhaustible source of RPE for the efficacious treatment of a range of retinal degenerative diseases.

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Section: Introductionmentioning

confidence: 99%

Long-Term Safety and Function of RPE from Human Embryonic Stem Cells in Preclinical Models of Macular Degeneration

et al. 2009

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“…8 -10 In contrast, RPE transplantation in animal models of retinal degeneration has been proved to rescue photoreceptors and to preserve visual acuity. [11][12][13][14][15][16] Although animal studies validate cell transplantation as a means of achieving photoreceptor rescue, important distinctions between humans with AMD and laboratory animals in which RPE transplantation has been successful include the age-and AMD-related modifications of the surface on which human RPE cells reside in situ (i.e., Bruch's membrane), which may have a significant effect on RPE graft survival. Evidence from human donor eye organ culture experiments indicates that healthy RPE cells cannot survive for an extended time on aged submacular Bruch's membrane, and the poorest survival is observed on AMD Bruch's membrane.…”

mentioning

confidence: 99%

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

Sugino¹,

Rapista²,

Sun³

et al. 2011

Invest. Ophthalmol. Vis. Sci.

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“…Retinal transplantation places sheets of developing retina and retinal pigment epithelial cells into the subretinal space [ 46 ]. Whereas adult transplants have been performed in humans with RP and age-related macular degeneration (AMD); [ 47 ] the transplants have not caused harm but there is no evidence that the cells of the transplanted tissue mingle with or develop synaptic connections. Radtke and his group reported efficacy and safety in implanting fetal retina with accompanying RPE in AMD and RP patients with vision of 20/200.…”

Section: Retinal Transplantationmentioning

confidence: 99%

Current Concepts in the Treatment of Retinitis Pigmentosa

Musarella

MacDonald

2011

Journal of Ophthalmology

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Inherited retinal degenerations, including retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA), affect 1 in 4000 individuals in the general population. A majority of the genes which are mutated in these conditions are expressed in either photoreceptors or the retinal pigment epithelium (RPE). There is considerable variation in the clinical severity of these conditions; the most severe being autosomal recessive LCA, a heterogeneous retinal degenerative disease and the commonest cause of congenital blindness in children. Here, we discuss all the potential treatments that are now available for retinal degeneration. A number of therapeutic avenues are being explored based on our knowledge of the pathophysiology of retinal degeneration derived from research on animal models, including: gene therapy, antiapoptosis agents, neurotrophic factors, and dietary supplementation. Technological advances in retinal implant devices continue to provide the promise of vision for patients with end-stage disease.

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Retinal Pigment Epithelium and Photoreceptor Transplantation Frontiers

Cited by 11 publications

References 268 publications

Long-Term Safety and Function of RPE from Human Embryonic Stem Cells in Preclinical Models of Macular Degeneration

Long-Term Safety and Function of RPE from Human Embryonic Stem Cells in Preclinical Models of Macular Degeneration

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

Current Concepts in the Treatment of Retinitis Pigmentosa

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