iPSC-RPE patch restores photoreceptors and regenerates choriocapillaris in a pig retinal degeneration model
Rohan Gupta, … , Juan Amaral, Kapil Bharti
Rohan Gupta, … , Juan Amaral, Kapil Bharti
Published May 22, 2025
Citation Information: JCI Insight. 2025;10(10):e179246. https://doi.org/10.1172/jci.insight.179246.
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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 1

Study and surgery design.

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Study and surgery design. (A) Animals were evaluated 7 days before surge...
(A) Animals were evaluated 7 days before surgery (day –7) using optical coherence tomography (OCT), OCT-angiography (OCT-A), and adaptive optics (AO). On the day of laser treatment (day 0), a 7 mm × 7 mm area within the visual streak was ablated with a micropulse laser. Two days after the laser injury, transplants were delivered into the subretinal space using standard vitreoretinal techniques. Animals were followed for up to 80 days. (B–G) Baseline (B, D, and F) and after laser injury (C, E, and G) fundus photographs (B and C), FA (D and E), and OCT (F and G) of the pig eye. Arrowheads in C, E, and G mark borders of the laser lesion. (H) Cannula tips containing PLGA only (bottom) and PLGA-iRPE (top) are marked by arrowheads. (I) Scleral clamp was used to secure the sclerotomy. (J–Q) Surgical technique for immediate sequential delivery of 2 transplants into the subretinal space: After vitrectomy, a 2.4 mm sclerotomy was created using a surgical knife (J); sclerotomy was sealed watertight using a clamp (K); retinal detachment was created by injecting 0.25% Healon BSS+ solution in the subretinal space (L); a 2.5–3 mm retinotomy was created using retinal scissors (M); the first cannula was introduced through the clamp (N) and transplant delivered subretinally (O); after withdrawal of the first cannula and wound securing with the clamp, the second cannula was introduced and transplant delivered (P); and retinal detachment was flattened using fluid-air exchange (Q).