TY - JOUR TI - Impaired ABCA1/ABCG1-mediated lipid efflux in the mouse retinal pigment epithelium (RPE) leads to retinal degeneration AU - Storti, Federica AU - Klee, Katrin AU - Todorova, Vyara AU - Steiner, Regula AU - Othman, Alaa AU - van der Velde-Visser, Saskia AU - Samardzija, Marijana AU - Meneau, Isabelle AU - Barben, Maya AU - Karademir, Duygu AU - Pauzuolyte, Valda AU - Boye, Sanford L AU - Blaser, Frank AU - Ullmer, Christoph AU - Dunaief, Joshua L AU - Hornemann, Thorsten AU - Rohrer, Lucia AU - den Hollander, Anneke AU - von Eckardstein, Arnold AU - Fingerle, Jürgen AU - Maugeais, Cyrille AU - Grimm, Christian A2 - Nathans, Jeremy A2 - Marder, Eve A2 - Radu, Roxana VL - 8 PY - 2019 DA - 2019/03/13 SP - e45100 C1 - eLife 2019;8:e45100 DO - 10.7554/eLife.45100 UR - https://doi.org/10.7554/eLife.45100 AB - Age-related macular degeneration (AMD) is a progressive disease of the retinal pigment epithelium (RPE) and the retina leading to loss of central vision. Polymorphisms in genes involved in lipid metabolism, including the ATP-binding cassette transporter A1 (ABCA1), have been associated with AMD risk. However, the significance of retinal lipid handling for AMD pathogenesis remains elusive. Here, we study the contribution of lipid efflux in the RPE by generating a mouse model lacking ABCA1 and its partner ABCG1 specifically in this layer. Mutant mice show lipid accumulation in the RPE, reduced RPE and retinal function, retinal inflammation and RPE/photoreceptor degeneration. Data from human cell lines indicate that the ABCA1 AMD risk-conferring allele decreases ABCA1 expression, identifying the potential molecular cause that underlies the genetic risk for AMD. Our results highlight the essential homeostatic role for lipid efflux in the RPE and suggest a pathogenic contribution of reduced ABCA1 function to AMD. KW - ABCA1 KW - retinal degeneration KW - retinal pigment epithelium KW - lipid efflux KW - age-related macular degeneration KW - ABCG1 JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -