A Subretinal Cell Delivery Method via Suprachoroidal Access in Minipigs: Safety and Surgical Outcomes

Abstract

PURPOSE. This study evaluated a new subretinal method for delivery of human or pig umbilical tissue-derived cells (hUTC or pUTC, respectively) using a novel subretinal injection cannula and suprachoroidal approach in Göttingen minipig eyes. hUTC (palucorcel) are currently under development for treating geographic atrophy in humans.METHODS. Twenty-four Göttingen minipigs (divided into eight groups) were subretinally administered palucorcel, pUTC, or vehicle. In some cases, fluorescently labeled cells and vehicle were administered. Conjunctival cutdown and sclerotomy were performed, then a flexible cannula containing a microneedle was inserted and advanced into the suprachoroidal space. The microneedle was deployed and visualized; 50 lL cells (target concentration, 11.2 3 10 6 cells/mL [560,000 cells/eye]) or vehicle was injected subretinally. Safety outcomes were evaluated.RESULTS. For all animals, cells and vehicle were successfully administered. Labeled cells or fluorescent vehicle were contained in the subretinal bleb, without leakage into the vitreous. No retinal detachment or vitreous traction band was identified by ophthalmologic examination. At all time points, observed microscopic changes were attributable to experimental procedures. On histopathology immediately after injection, localized retinal detachments were seen, along with focal retinal, choroidal, and/or scleral discontinuities. A moderate inflammatory response was seen in a limited number of animals. In the allogeneic setting, no antibody responses were detectable. Anti-human UTC antibodies were detected in the xenogeneic setting.CONCLUSIONS. Palucorcel, pUTC, and vehicle were successfully administered to Göttingen minipigs using a novel subretinal injection cannula via a suprachoroidal surgical approach, with no significant adverse events; therefore, this technique appears to be feasible for further clinical development.

Current Clinical Applications of In Vivo Gene Therapy with AAVs

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Where Are We with RPE Replacement Therapy? A Translational Review from the Ophthalmologist Perspective

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“…Kashani [28,29]. De Smet et al präsentierten im Jahr 2017 ein neues Injektionssystem, das bei einer weiteren geplanten multizentrischen Phase-II-Sicherheitsstudie getestet werden soll (NCT02659098) [30].…”