July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Efficacy of clinical-grade iPSC-RPE cells and patch in rodent and swine models of retinal degeneration
Author Affiliations & Notes
  • Aaron Rising
    National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
  • Vladimir Khristov
    National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
  • Yichao Li
    National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
  • Maria M Campos
    National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
  • Haohua Qian
    National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
  • Jonathan Stoddard
    Opthalmology, Casey Eye Institute-OHSU, Beaverton, Oregon, United States
  • Arvydas Maminishkis
    National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
  • Juan Amaral
    National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
  • Trevor J McGill
    Opthalmology, Casey Eye Institute-OHSU, Beaverton, Oregon, United States
  • Sheldon S Miller
    National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
  • Kapil Bharti
    National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
  • Footnotes
    Commercial Relationships   Aaron Rising, None; Vladimir Khristov, None; Yichao Li, None; Maria Campos, None; Haohua Qian, None; Jonathan Stoddard, None; Arvydas Maminishkis, None; Juan Amaral, None; Trevor McGill, None; Sheldon Miller, None; Kapil Bharti, None
  • Footnotes
    Support  IRP NIH & Common Fund NIH
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 546. doi:
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      Aaron Rising, Vladimir Khristov, Yichao Li, Maria M Campos, Haohua Qian, Jonathan Stoddard, Arvydas Maminishkis, Juan Amaral, Trevor J McGill, Sheldon S Miller, Kapil Bharti; Efficacy of clinical-grade iPSC-RPE cells and patch in rodent and swine models of retinal degeneration. Invest. Ophthalmol. Vis. Sci. 2018;59(9):546.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Age-related macular degeneration (AMD) causes progressive visual loss in people 50 years and older with approximately 200,000 new cases per year in the United States. Advanced AMD stages are thought to be triggered by degeneration of retinal pigmented epitheial (RPE) monolayer in the back of the eye. RPE replacement has been suggested as a pontetial therapy for AMD. The goal of this study is to determine the efficacy of human induced pluripotent stem derived RPE (iRPE) cells delivered in the subretinal space on a biodegradable scaffold or as a suspension in a rodent and swine model of retinal degeneration.

Methods : A 0.5 mm diameter iRPE-patch on a biodegradable scaffold or iRPE-cell suspension (100,000 cells) was placed subretinally in Royal College of Surgeion (RCS) rats at day p28. Optokinetic (OKN) measurement testing was performed before implantation and at p60 and p90. In a pig eye with laser ablation of the RPE, a 4x2 mm scaffold with or without iRPE cells, or iRPE-cell suspension was placed in the sub-retinal space. Subsequent multi-focal electroretinography (mfERG) recordings were performed and 7 different mfERG components (N1, P1, N1P1, Area Under the Curve, Scalar Product, N1 width and P1 width) to were calculated to assess the efficacy of the implants. Linear regression and linear mixed model analysis was performed to determine statistical significance (a p<0.05 value was deemed significant). Histology was performed after the final functional tests.

Results : In RCS rats, cells in suspension showed higher OKN responses at p60 as compared to vehicle control or iRPE-patch. At p90, both iRPE-patch and iRPE-cells showed similar OKN responses and higher than controls. Histology confirmed a protected photoreceptor layer over the iRPE-cells and iRPE-patch. In the swine model, the scaffold with cells showed significant improvements over the scaffold without cells and to cell in suspension when combining 7 mfERG components in a linear mixed model analysis. Several of these components showed significant differences when analyzed by linear regression. Histology confirmed integration of iRPE-patch and improved retinal morphology.

Conclusions : Our results show that in two retinal degeneration animal models, aiRPE-patch can significantly improve functionality. In both models, the implant integrates in the back of the eye on top of the Bruch’s membrane and with the adjacent native RPE.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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