Establishing a Surgical Procedure for Rhesus Epiretinal Scaffold Implantation with HiPSC-Derived Retinal Progenitors

Abstract

Background To develop an effective surgical procedure for cellular scaffold epiretinal implantation in rhesus, facilitating subsequent epiretinal stem cell transplantation. Methods Retinal progenitors were seeded onto a poly(lactic-co-glycolic) acid (PLGA) scaffold. First, the cellular scaffolds were delivered by 18G catheter or retinal forceps into rabbit epiretinal space (n = 50). Then, the cell survival rate was evaluated by Cell Counting Kit-8 (CCK-8). Second, three methods of scaffold fixation, including adhesion after gas-liquid exchange (n = 1), tamponade by hydrogel (n = 1), and fixation by retinal tacks (n = 4), were performed in rhesus monkeys. After one month, fundus photography and SD-OCT were performed to assess the outcomes, and histological examination was performed to evaluate proliferation. Results The cell survival rate was significantly higher in the catheter group. Follow-up examination showed that retinal tack fixation was the only method to maintain the scaffolds attached to host retina for at least 3 weeks, which is the minimal time required for cell integration. Histological staining demonstrated slight glial fibrillary acidic protein (GFAP) accumulation in the retinal tack insertion area. Conclusions The established surgical procedure offers a new insight into research of epiretinal cell replacement therapy in rhesus eyes. The successful delivery and long-term fixation provide a prerequisite for cell migration and integration.

Islet1 and Brn3 Expression Pattern Study in Human Retina and hiPSC-Derived Retinal Organoid

“…The retinoblastoma tissue was collected by Prof. Rong Lu. Rhesus slices were collected from the control eyes of a previous study [13]. All samples were collected with patient consents and in accordance with protocols approved by the institutional review boards at Zhongshan Ophthalmic Center, SYSU (approval number: 2013PRLL0029).…”

Development of a Graphene Oxide-Incorporated Polydimethylsiloxane Membrane with Hexagonal Micropillars

“…Scaffold fixation in damaged tissue is one of the prerequisites of successful transplantation. Stable positioning of transplants enhances the cell-to-microenvironment interaction, cell biological activity, and cell survival [ 40 ]. In the present study, we sought to incorporate suture-free fixation capacity into the developed GO-enriched PDMS scaffold with GO coating (PDMS/GO + GO) for application in nonsuturable tissue.…”

Dexamethasone Provides Effective Immunosuppression for Improved Survival of Retinal Organoids after Epiretinal Transplantation

“…The retinal transplantation surgeries were performed on three OHT eyes and one healthy eye according to the protocol described by Luo et al [6]. All surgical procedures were performed by the same surgeon.…”

“…Our research team has previously established a new surgical procedure for transplanting retinal organoids as sheets into rhesus monkey eyes [6]. However, although this procedure was successful for the placement and long-term fixation of an epiretinal transplant, the presence of pathological lesions at the transplantation site and the inevitable injuries inflicted during surgery might activate innate immunocytes and impede the survival and integration of grafted cells [7].…”