Evaluating Retinal Transplantation Success in Degenerated RCS Nude Rats Using Electroretinography

Our research aims to develop a therapy for incurable retinal diseases, such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD), using the retinal degenerate Royal College of Surgeons (RCS) nude rat model. The approach involves transplanting human embryonic stem cell (hESC)-derived retinal organoid sheets. Photoreceptors in RCS nude rats deteriorate over time, leading to impaired vision, similar to RP and AMD. By transplanting hESC-derived retinal organoid sheets, the degenerated host photoreceptors may be replaced or rescued, potentially halting further degeneration and even enhancing visual performance. Electroretinography (ERG), a noninvasive method, is used to measure visual function. Our current project utilizes ERG to monitor visual responses in RCS nude rats and test whether transplantation of hESC-derived sheets leads to improved light response compared to age-matched control (AMC) non-surgery and sham groups. The left eyes of RCS nude rats were exclusively treated with retinal sheet transplants, allowing for internal comparison. ERG data collected every two months over six months showed a significant decline in visual function with age in both low-light scotopic and bright-light photopic tests for AMC and sham groups. Notably, transplanted RCS nude rats exhibited enhanced responses in the treated left eyes. Together with findings from superior colliculus (SC) recordings and Optokinetic (OKN) assessments, the results suggest that hESC-derived retinal organoid sheets improve visual function in RCS nude rats.