In:
eLife, eLife Sciences Publications, Ltd, Vol. 8 ( 2019-03-13)
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.45100.001
DOI:
10.7554/eLife.45100.002
DOI:
10.7554/eLife.45100.003
DOI:
10.7554/eLife.45100.004
DOI:
10.7554/eLife.45100.005
DOI:
10.7554/eLife.45100.006
DOI:
10.7554/eLife.45100.007
DOI:
10.7554/eLife.45100.010
DOI:
10.7554/eLife.45100.008
DOI:
10.7554/eLife.45100.009
DOI:
10.7554/eLife.45100.011
DOI:
10.7554/eLife.45100.012
DOI:
10.7554/eLife.45100.013
DOI:
10.7554/eLife.45100.014
DOI:
10.7554/eLife.45100.015
DOI:
10.7554/eLife.45100.016
DOI:
10.7554/eLife.45100.017
DOI:
10.7554/eLife.45100.018
DOI:
10.7554/eLife.45100.019
DOI:
10.7554/eLife.45100.020
DOI:
10.7554/eLife.45100.021
DOI:
10.7554/eLife.45100.022
DOI:
10.7554/eLife.45100.023
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2019
detail.hit.zdb_id:
2687154-3
