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More and more patients suffer from multifactorial neurodegenerative diseases, such as age-related macular degeneration (AMD). However, their pathological mechanisms are still poorly understood, which complicates the development of effective therapies. To improve treatment of multifactorial diseases, cell-based gene therapy can be used to increase the expression of therapeutic factors. To date, there is no approved therapy for dry AMD, including late-stage geographic atrophy. We present a treatment option for dry AMD that transfers the brain-derived neurotrophic factor (<i>BDNF</i>) gene into retinal pigment epithelial (RPE) cells by electroporation using the plasmid-based <i>Sleeping Beauty</i> (<i>SB</i>) transposon system. ARPE-19 cells and primary human RPE cells were co-transfected with two plasmids encoding the <i>SB100X</i> transposase and the transposon carrying a <i>BDNF</i> transcription cassette. We demonstrated efficient expression and secretion of BDNF in both RPE cell types, which were further increased in ARPE-19 cell cultures exposed to hydrogen peroxide. BDNF-transfected cells exhibited lower apoptosis rates and stimulated neurite outgrowth in human SH-SY5Y cells. This study is an important step in the development of a cell-based <i>BDNF</i> gene therapy that could be applied as an advanced therapy medicinal product to treat dry AMD or other degenerative retinal diseases.