Feasibility of a double dose of iPSC-RPE patch transplantation in a laser-induced RPE ablation swine model

Abstract

Purpose : Retinal Pigment epithelium (RPE) cell-based therapy is being tested for degenerative retinal diseases with the goal of replacing atrophied RPE cells for restoration of degenerating photoreceptors. To compare transplants side-by-side (empty scaffold/RPE-patch), and develop double dose of RPE-patch, we tested the feasibility of delivering two transplants while minimizing surgical damage.

Methods : A micro pulse laser was used to selectively ablate RPE cells in Yucatan minipigs leading to outer retinal degeneration. A custom-made injector was used for PLGA/RPE-patch delivery. Nine surgeries were performed with follow-ups up to 23 weeks (OCT/ angiography). In five cases, a custom-made clamp closed the scleral wound between maneuvers. Perfluoro Octane (PFO) was used in 5 cases to protect the retina during the sclerotomy. In 3 cases a subretinal cannula was used to extend the size of the retinal detachment (RD)

Results : In all cases both (empty PLGA and PLGA-RPE) transplants were successfully delivered. In cases where no clamp was used, turbulence and hypotony made maneuvers difficult. Hypotony was associated with poor prognosis as noted in follow-ups. In one case with bleeding from the sclerotomy, PFO protected the retina making it easier to aspirate blood. In cases with subretinal cannula use, two developed post-surgical vitreous hemorrhage. One developed RD; the other developed extensive retinal fibrosis and tractional RD. Five cases developed an inflammatory reaction below the RPE-patch not the empty scaffold, suggesting reaction to xeno-cells, confirmed by OCT and angiography. In four cases methotrexate (MTX) was used intravitreally to resolve the inflammation; three cases responded to a single injection.

Conclusions : Our custom-made clamp prevented complications secondary to turbulence and hypotony while PFO protected the retina when there was bleeding from the sclerotomy. Sub-retinal cannula use should be minimized to prevent extensive retinal damage. MTX was effective in controlling inflammatory reactions secondary to xeno-cell transplantation.
Successful delivery of two patches demonstrated feasibility of the technique, opening the possibility of treating larger areas of retinal degeneration. Lessons learned can be applied to minimize surgical and post-surgical complications.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.