Abstract
Purpose :
Stargardt disease is the most prevalent juvenile-onset inherited maculopathy. Defects in the gene ABCA4 lead to accumulation of toxic vitamin A derivatives in cells of the retinal pigment epithelium (RPE), causing RPE dysfunction and degeneration. Retinal function may be protected or promoted by provision of a replenished population of RPE cells. Human embryonic stem cells (hESCs) provide one source of RPE cells for transplantation. Our aim was to investigate the safety and tolerability of subretinal transplantation of a suspension of hESC-derived RPE cells in advanced Stargardt disease.
Methods :
We included 12 participants (aged 34 - 45 years) with clinical and electroretinographic features of advanced Group 3 Stargardt disease. Following pars plana vitrectomy we injected subretinally a suspension of hESC-derived RPE cells at doses of 50 K, 100 K, 150 K and 200 K cells. Participants were administered systemic immunosuppression until 3 months after the transplant procedure. We assessed systemic and ocular safety, indicators of cell survival and retinal function for 12 months.
Results :
We observed the development of areas of subretinal hyperpigmentation in all participants, suggesting survival and engraftment of hESC-derived RPE cells. The extent of hyperpigmentation correlated positively with the dose of cells administered (R2=0.58, p<0.05). Hyperpigmentation was associated with areas of both hypo- and hyper-autofluorescence. We identified no evidence of tumorigenicity, immune adverse events or other serious safety concerns related to the transplanted cells. Assessment of ETDRS visual acuity, microperimetry, static full field perimetry, colour vision testing and electoretinography demonstrated no significant loss of visual function in the study eye of any participant.
Conclusions :
Subretinal transplantation of hESC-derived RPE cells in Stargardt disease appears safe and well tolerated up to 12 months. The favourable safety profile supports the prospect of further studies to investigate the potential for benefit in less advanced disease.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.