Harvesting RPE for culture and subsequent retransplantation

SUMMARY: The rationale is to develop protocols for using a patient`s own retinal pigment epithelium (RPE) to replace degenerated cells in age-related macular degeneration (AMD), the leading cause of blindness over 50 years of age. The proposed study aims to grow a surgical tissue sample of RPE in culture and then investigate transplantation into living eyes. BACKGROUND: The RPE serves as a metabolic filter unit between the retina and the choroid. It has been suggested, that over lifetime cumulative damage to the RPE leads to the manifestation of AMD. Therefore replacement of degenerate cells is an attractive strategy. Only a minority of these patients is currently eligible for palliative, conventional therapies. Our group has already established a technique for transplanting a patient`s own RPE cells. However, only a limited amount of cells can obtained, and lesion coverage is insufficient. Furthermore, the fate of the transplanted cells in the lesioned area is uncertain. This application proposes as a possible solution the idea of cell culture as an intermediate step. A small sample of RPE cells can expand in culture to generate enough cells to cover an AMD lesion. Such cells would be transferred on a carrier matrix and delivered back into eye of the same patient. METHODS: Initially a culture system for aged human RPE on model systems of Bruch`s membrane will be established. The cultures will be screened for in vivo resemblance to normal RPE by testing various physiologic characteristics. We will then attempt to grow RPE from surgical tissue samples. A carrier matrix for transplantation will be seeded with the cells and the RPE tested again for physiological properties and long term performance. RELEVANCE: The prevalence of AMD is about 20% in the population over 65 years old. Most patients have no therapeutic option. The development of an effective RPE transplantation technique offers a potentially curative treatment.