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Yichao Li, Juan Amaral, Raymond Zhou, Arvydas Maminishkis, Sheldon S Miller, Haohua Qian, Kapil Bharti; Functional Evaluation of Subretinal Space iPSC-RPE Implant In a Laser-Induced RPE Injury Model In Pig. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3754.
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© ARVO (1962-2015); The Authors (2016-present)
Age-related macular degeneration (AMD) is a global disease for which there is no cure. Malfunction of RPE cells is the primary cause of disease progression. Replacing diseased or dead RPE cells may provide an effective approach for the treatment for AMD. In this study, we investigated the regenerative effect of induced pluripotent stem cell (iPSC)-RPE implants in a pig model of laser-induced RPE damage.
Pigs at 2-3-months of age were used in this study. Microsecond pulse laser was used to generate the RPE injury model. Subretinal iPSC-RPE was surgically implanted 2 days after laser treatment. Fundus images were acquired with Heidelberg Spectralis OCT. Multifocal ERG (mfERG) responses were recorded with RETImap (Roland Consultant). Responses from the implant and laser-damaged areas were normalized relative to those elicited from healthy part of the retina.
Subretinal iPSC-RPE implants, visualized on by OCT at follow-up examination after surgery, showed that Bruch’s membrane was intact and that the inner retinal layers were healthy. At post-surgery day (PSD) 7, the implant complex thickness (measured from Bruch’s membrane to the end of the implant) had an average thickness of 117.14 ± 12.26 μm (n = 7). By PSD 28 and PSD 35, the implant complex began to show decreasing of thickness; by PSD 42 the implant showed signs of disintegration and measured a mean thickness of 69 ± 4.58 μm (n = 7). mfERG responses from both implant-area and laser-damage area showed gradual recovery. Linear regression of mfERG amplitude yielded similar y-intercepts (0.48) for responses elicited from these two regions, consistent with laser-induced uniform retinal damage. On the other hand, the responses recorded from the implant-area exhibited a larger slope than those elicited from laser-only area, suggesting an accelerated retinal functional recovery following the iPSC-RPE implant.
OCT images revealed that the iPSC-RPE implant was integrated in the subretinal space as necessary for the functional recovery of the retina. mfERG responses from the laser area with implant showed a significant improvement compared to the laser-only area. In this pre-clinical model the minimal invasiveness of the iPSC-RPE implant and it ability to regenerate retinal function suggests a promising future for the restoration of retinal function in AMD patients.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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