Helen L Winton

Subretinal transplantation of genetically modified human cell lines attenuates loss of visual function in dystrophic rats

Royal College of Surgeons rats are genetically predisposed to undergo significant visual loss caused by a primary dysfunction of retinal pigment epithelial (RPE) cells. By using this model, we have examined the efficacy of subretinal transplantation of two independent human RPE cell lines each exhibiting genetic modifications that confer long-term stability in vitro. The two cell lines, a spontaneously derived cell line (ARPE19) and an extensively characterized genetically engineered human RPE cell line (h1RPE7), which expresses SV40 large T (tumor) antigen, were evaluated separately. Both lines result in a significant preservation of visual function as assessed by either behavioral or physiological techniques. This attenuation of visual loss correlates with photoreceptor survival and the presence of donor cells in the areas of rescued photoreceptors at 5 months postgrafting (6 months of age). These results demonstrate the potential of genetically modified human RPE cells for ultimate application in therapeutic transplantation strategies for retinal degenerative diseases caused by RPE dysfunction.

Corneal transplant follow-up study II (CTFS II): a prospective clinical trial to determine the influence of HLA class II matching on corneal transplant rejection: baseline donor and recipient characteristics

Purpose To describe a study to determine the influence of HLA class II matching on allograft rejection of high-risk, full-thickness corneal transplants. Methods A prospective, longitudinal, clinical trial (ISRCTN25094892) with a primary outcome measure of time to first clinically determined rejection episode. Tissue typing used DNA-based techniques. Corneas were allocated to patients with ≤2 human leucocyte antigen (HLA) class I antigen mismatches by cohort minimisation to achieve 0, 1 or 2 HLA class II (HLA-DR) antigen mismatches. Transplants were to be followed up at 6 months and then annually on the anniversary of surgery for 5 years. Power calculations estimated a sample size of 856 transplants to detect a 0.1 difference in probability of rejection at 1 year between HLA class II matched and mismatched transplants at the 5% level of significance with 80% power. Results To allow for loss to follow-up, 1133 transplants in 980 patients were accrued to the study between 3 September 1998 and 2 June 2011. 17% of transplants had 0 HLA-DR mismatches. The most frequent indication was bullous keratopathy, accounting for 27% of transplants and 54% of the transplants were regrafts. Median waiting time for a matched graft was 3 months. Donor and recipient characteristics were distributed evenly across the study groups. Conclusion Recruitment to the CFS II has closed with 1077/1133 transplants meeting all the study criteria. Follow-up has been completed and final analysis of the data has started. Trial registration number ISRCTN25094892 andUKCRNID9871, Pre-results.