Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. Wet AMD is characterised by choroidal neovascularisation, new vessels into the retina, leading to leakage and tissue damage. Many proangiogenic factors particularly vascular endothelial growth factor (VEGF) are fundamental to neovascularisation as shown by several drugs that block this pathway being used in AMD treatment. Fibulin-5 (Fbln5) is a matrix glycoprotein expressed in the retina and mutations in Fbln5 gene have been associated with increased risk of developing AMD. Fbln5 is an inhibitor of VEGF, a function that may explain the genetic data. In this paper retinal pigment epithelium cells were transfected with a lentivirus construct containing the FBln5 and GFP, such that the resultant cells overexpressed the protein and were green on fluorescence microscopy. CNV was induced by laser photocoagulation in rats and Fbln5-transfected RPE cells or RPE cells with the same construct, minus FBLn5, were injected into the subretinal space of the right and left eyes respectively. Transplanted RPE cells survived for at least four weeks, and eyes with Fbln5 overexpressing RPE cells showed a significantly smaller area of leakage and number of leakage spots compared to eyes transfected with control RPE cells. Growth and injection of RPE cells cultivated in vitro show promise for the treatment of AMD. This study demonstrates that manipulation of RPE cells prior to delivery to the eye can enhance the effect of such cells and provides a new area of research to define which genes will give the best results. This may depend on the potential to make stable contrasts to avoid continuous treatment, but the concept shown is important.