Long term visual and microperimetry outcomes following autologous retinal pigment epithelium choroid graft for neovascular age-related macular degeneration

FK, Chen; Uppal, Gurmit; MacLaren, R E; Coffey, PJ; Rubin, GS; Tufail, Adnan; Aylward, G W; Cruz, L Da

doi:10.1111/j.1442-9071.2008.01915.x

Cited by 10 publications

(7 citation statements)

References 24 publications

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“…Because the etiology of AMD is still under investigation, one focus of therapy has been on replacing diseased RPE through transplantation [4]. The feasibility of this approach has been demonstrated by autologous replacement of RPE in the macula, the central portion of the retina responsible for high acuity vision, via macular translocation or relocation of peripheral RPE to the macula [5–7]. Although somewhat effective, these surgeries are long and complicated.…”

Section: Introductionmentioning

confidence: 99%

Rapid and Efficient Directed Differentiation of Human Pluripotent Stem Cells Into Retinal Pigmented Epithelium

Buchholz

Pennington

Croze

et al. 2013

Stem Cells Translational Medicine

232

208

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Controlling the differentiation of human pluripotent stem cells is the goal of many laboratories, both to study normal human development and to generate cells for transplantation. One important cell type under investigation is the retinal pigmented epithelium (RPE). Age-related macular degeneration (AMD), the leading cause of blindness in the Western world, is caused by dysfunction and death of the RPE. Currently, RPE derived from human embryonic stem cells are in clinical trials for the treatment of AMD. Although protocols to generate RPE from human pluripotent stem cells have become more efficient since the first report in 2004, they are still time-consuming and relatively inefficient. We have found that the addition of defined factors at specific times leads to conversion of approximately 80% of the cells to an RPE phenotype in only 14 days. This protocol should be useful for rapidly generating RPE for transplantation as well as for studying RPE development in vitro.

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Section: Introductionmentioning

confidence: 99%

Rapid and Efficient Directed Differentiation of Human Pluripotent Stem Cells Into Retinal Pigmented Epithelium

Buchholz

Pennington

Croze

et al. 2013

Stem Cells Translational Medicine

232

208

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“…For the more common dry or nonexudative form of AMD, there is no effective treatment option to date [16]. Autologous transplantation of RPE/choroid from the periphery of the eye to the macula has demonstrated the potential for RPE cell replacement as a therapy for AMD [18–24]. Use of iPSC‐derived RPE (iPS‐RPE) as a therapy would reduce surgical complexity and maintain the benefit of immune‐matched autologous cells.…”

Section: Introductionmentioning

confidence: 99%

Derivation of Functional Retinal Pigmented Epithelium from Induced Pluripotent Stem Cells

et al. 2009

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Human induced pluripotent stem cells (iPSCs) have great promise for cellular therapy, but it is unclear if they have the same potential as human embryonic stem cells (hESCs) to differentiate into specialized cell types. Ocular cells such as the retinal pigmented epithelium (RPE) are of particular interest because they could be used to treat degenerative eye diseases, including age-related macular degeneration and retinitis pigmentosa. We show here that iPSCs generated using Oct4, Sox2, Nanog, and Lin28 can spontaneously differentiate into RPE cells, which can then be isolated and cultured to form highly differentiated RPE monolayers. RPE derived from iPSCs (iPS-RPE) were analyzed with respect to gene expression, protein expression, and rod outer segment phagocytosis, and compared with cultured fetal human RPE (fRPE) and RPE derived from hESCs (hESC-RPE). iPS-RPE expression of marker mRNAs was quantitatively similar to that of fRPE and hESC-RPE, and marker proteins were appropriately expressed and localized in polarized monolayers. Levels of rod outer segment phagocytosis by iPS-RPE, fRPE, and hESC-RPE were likewise similar and dependent on integrin avb5. This work shows that iPSCs can differentiate into functional RPE that are quantitatively similar to fRPE and hESC-RPE and further supports the finding that iPSCs are similar to hESCs in their differentiation potential.

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“…A limitation of the procedure, however, is the surgical morbidity, with a high proportion of patients undergoing repeat surgery because of PVR, macular pucker, retinal detachment or vitreous haemorrhage 10 11. In one series, there was also evidence of further loss of function, possibly related to the initial trauma of surgery 28. Unless modifications can be made to reduce the surgical complexity and risks involved in full-thickness RPE-choroid grafts, the applicability of this procedure is likely to remain limited when compared to the new medical therapies currently being developed.…”

Section: Morphology and Function Of The Rpe–bruch's Interfacementioning

confidence: 99%

Sources of retinal pigment epithelium (RPE) for replacement therapy

Lee

MacLaren

2010

British Journal of Ophthalmology

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Stem cells, with their capacity to regenerate and replace diseased tissues, have recently been proposed as having great potential in the treatment of age-related macular degeneration (AMD). A stem cell therapeutic approach could operate to replace either the retinal pigment epithelium (RPE), the neurosensory retina or a combination of both. From the scientific perspective, RPE replacement alone is likely to be far more straightforward than rebuilding the complex circuitry of the neurosensory retina. Furthermore, recent advances with induced pluripotent stem cells have raised the real possibility of transplanting healthy 'young' autologous RPE into patients with early signs of AMD. At this stage, however, it is useful to reconsider some of the earlier clinical studies that used suspensions of autologous RPE cells harvested from the peripheral retina. These showed that isolated RPE cell suspensions had little capacity to recreate a monolayer on the diseased Bruch's membrane of AMD. To counter this problem, researchers from Southampton in the UK report the use of a synthetic polymer alternative to Bruch's membrane, which could provide a scaffold for future RPE derived from stem cells or possibly reopen opportunities for autologous RPE cells harvested from the peripheral retina.

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Long term visual and microperimetry outcomes following autologous retinal pigment epithelium choroid graft for neovascular age-related macular degeneration

Cited by 10 publications

References 24 publications

Rapid and Efficient Directed Differentiation of Human Pluripotent Stem Cells Into Retinal Pigmented Epithelium

Rapid and Efficient Directed Differentiation of Human Pluripotent Stem Cells Into Retinal Pigmented Epithelium

Derivation of Functional Retinal Pigmented Epithelium from Induced Pluripotent Stem Cells

Sources of retinal pigment epithelium (RPE) for replacement therapy

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