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Aaron Rising, Yichao Li, Vladimir Khristov, Balendu Jha, Haohua Qian, Maria M Campos, Arvydas Maminishkis, Juan Amaral, Sheldon S Miller, Kapil Bharti; Human iPSC-RPE cell transplant in a swine laser-injury model mitigates progressive visual functionality decline.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1992. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Age-related macular degeneration (AMD) is a progressive eye disorder that causes visual loss in people 50 years and older with 200,000 new cases per year in the United States. Our goal is to mitigate the functional visual decline in a laser-induced RPE injury in pigs with induced pluripotent cells derived retinal pigmented epithelial (iPSC-RPE).
We use a swine model, because pig eye size and anatomy is similar to human’s, making it easier to translate results to the clinic. To generate our AMD-like model the pig RPE is laser-injured. After surgically introducing the iPSC-RPE cells on a permeable and biodegradable scaffold implant we measure the visual functionality by multi-focal electroretinography (mfERG)and in vivo anatomical architectures using optical coherence tomography (OCT) out to 10 weeks. For the mfERG assessments, we measured the N1P1 signal at each time point. The N1P1 signal differential between implant and the laser signal was calculated and used as main functional measurement. Histological assessments including H&E, Masson and immunohistochemistry were preformed to determine rescue of the retina by the iPSC-RPE implant. A total of 8 experimental and 6 control male swine eyes were used for this study. Statistical significance was determined using 2-way ANOVA at p<0.05.
RPE injury leads to progressive photoreceptor cell death and a decreased retinal response as measured by mfERG. Human iPSC-RPE cells survive under the retina of an immunosuppressed pig. The RPE monolayer on a scaffold is able to help rescue the dying photoreceptors, whereas the scaffold alone is not capable of this rescue as effectively. mfERG signal responses show statistically significant difference between implant with and without the RPE monolayer (p<0.05, 2-Way ANOVA). OCT and histology show that the retinal architecture above the implant with cells were better preserved compared to the retina above the implant without cells.
Our results show a statistically significant difference between the implant with and without iPSC-RPE cells. Both treatments show a decline of retinal function over time, however the treatment with iPSC-RPE cells mitigates the decline seen in the implant without cells. These feasibility studies lay the ground-work for GLP studies to test efficacy of clinical-grade iPSC-RPE derived from AMD patients.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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