Abstract
Purpose :
Chronic inflammation is now regarded as a major pathogenic pathway common in retinal degenerative diseases. Current studies suggest that antioxidant therapies for chronic inflammation treatment are a feasible objective to stop disease progression and represent a promising strategy to improve the therapeutic benefits of regenerative medicine. In this line, nanoceria has been added to the group of antioxidant/anti-inflammatory substances with therapeutic properties. Nanoceria has a unique electronic structure that when reduced to the nanoscale behaves as an oxygen radical scavenger. Here, we developed a new generation of functional nanomedicine which integrates single and combined therapeutic functions involving nanoceria, specially designed for an eye drop formulation, together with retinal pigment epithelial (RPE) cell therapy for retinal degeneration.
Methods :
Subretinal implantation of hiPSC-derived RPE cells in RCS rat model of retinitis pigmentosa was performed in the presence or absence of nanoceria eye drops. Four study groups were created: group 1 received subretinal injection of RPE cell suspension (10^5 cells/eye) under continuous nanoceria treatment; group 2 only received subretinal injection of RPE cell suspension; group 3 was injected with vehicle and treated with nanoceria; group 4 was injected with vehicle. Animals were tested at 1, 2, and 4 weeks after cell injection/treatment by OCT, FAF, and ERG to evaluate: 1) conservation of retina; 2) retinal function; 3) survival and integration of the implanted cells. After 4 weeks, animals were euthanized and eyes analyzed by ICP-MS, immunohistochemistry, qPCR, and western-blot.
Results :
Ocular administration of nanoceria eye drops in the RCS rats reaches all eye parts without translocation inside the body. Nanoceria preserved the retina structure and RPE viability after transplantation and decreased the infiltration of activated microglia and reduced reactive gliosis. Transplanted RPE cells in presence of nanoceria expressed higher levels of specific markers bestrophin 1, MITF, and RPE65, and reduced glial activation. Moreover, transplanted RPE with nanoceria better preserved ONL compared to vehicle treatment
Conclusions :
The combined therapy with RPE cell transplantation and the antioxidant and anti-inflammatory effect of the nanoceria eye drops is a potentially better therapeutic approach to protect the retina from degeneration.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.