iPSC-RPE patch restores photoreceptors and regenerates choriocapillaris in a pig retinal degeneration model
Rohan Gupta, Irina Bunea, Bruno Alvisio, Francesca Barone, Rishabh Gupta, Dara Baker, Haohua Qian, Elena Daniele, Casey G. Contreary, Jair Montford, Ruchi Sharma, Arvydas Maminishkis, Mandeep S. Singh, Maria Teresa Magone De Quadros Costa, Amir H. Kashani, Juan Amaral, Kapil Bharti
Rohan Gupta, Irina Bunea, Bruno Alvisio, Francesca Barone, Rishabh Gupta, Dara Baker, Haohua Qian, Elena Daniele, Casey G. Contreary, Jair Montford, Ruchi Sharma, Arvydas Maminishkis, Mandeep S. Singh, Maria Teresa Magone De Quadros Costa, Amir H. Kashani, Juan Amaral, Kapil Bharti
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Research Article Ophthalmology Transplantation

iPSC-RPE patch restores photoreceptors and regenerates choriocapillaris in a pig retinal degeneration model

Abstract

Dry age-related macular degeneration (AMD) is a leading cause of untreatable vision loss. In advanced cases, retinal pigment epithelium (RPE) cell loss occurs alongside photoreceptor and choriocapillaris degeneration. We hypothesized that an RPE-patch would mitigate photoreceptor and choriocapillaris degeneration to restore vision. An induced pluripotent stem cell–derived RPE (iRPE) patch was developed using a clinically compatible manufacturing process by maturing iRPE cells on a biodegradable poly(lactic-co-glycolic acid) (PLGA) scaffold. To compare outcomes, we developed a surgical procedure for immediate sequential delivery of PLGA-iRPE and/or PLGA-only patches in the subretinal space of a pig model of laser-induced outer retinal degeneration. Deep learning algorithm-based optical coherence tomography (OCT) image segmentation verified preservation of the photoreceptors over the areas of PLGA-iRPE–transplanted retina and not in laser-injured or PLGA-only–transplanted retina. Adaptive optics imaging of individual cone photoreceptors further supported this finding. OCT-angiography revealed choriocapillaris regeneration in PLGA-iRPE– and not in PLGA-only–transplanted retinas. Our data, obtained using clinically relevant techniques, verified that PLGA-iRPE supports photoreceptor survival and regenerates choriocapillaris in a laser-injured pig retina. Sequential delivery of two 8 mm2 transplants allows for testing of surgical feasibility and safety of the double dose. This work allows one surgery to treat larger and noncontiguous retinal degeneration areas.

Authors

Rohan Gupta, Irina Bunea, Bruno Alvisio, Francesca Barone, Rishabh Gupta, Dara Baker, Haohua Qian, Elena Daniele, Casey G. Contreary, Jair Montford, Ruchi Sharma, Arvydas Maminishkis, Mandeep S. Singh, Maria Teresa Magone De Quadros Costa, Amir H. Kashani, Juan Amaral, Kapil Bharti

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Figure 2

OCT evaluation of PLGA-iRPE and PLGA-only transplants in laser-injured porcine retinas.

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OCT evaluation of PLGA-iRPE and PLGA-only transplants in laser-injured p...
(A) Fundus infrared image of a pig eye at T1, with lasered region marked with blue lines, transplant boundaries marked with orange dotted lines, and the OCT scan position overlaid with the green line. (B) OCT B-scan of a pig retina at T1 showing the entire retinal region. Lasered region boundaries are marked with blue dotted lines. Transplants are marked with arrowheads, and their borders are delineated with orange dotted lines. INL, inner nuclear layer; ONL, outer nuclear layer. (C–J) Higher magnification image of OCT B-scan of untreated retina region at longitudinal time points T1 (C) and T2 (G); lasered region at T1 (D) and T2 (H); PLGA-iRPE–transplanted region at T1 (E) and T2 (I); and PLGA-only–transplanted region at T1 (F) and T2 (J).