Lack of Paraoxonase 1 Alters Phospholipid Composition, but Not Morphology and Function of the Mouse Retina

Oczos, Jadwiga; Sutter, Iryna; Kloeckener-Gruissem, Barbara; Berger, Wolfgang; Riwanto, Meliana; Rentsch, Katharina; Hornemann, Thorsten; Eckardstein, Arnold von; Grimm, Christian

doi:10.1167/iovs.14-14332

Cited by 6 publications

(4 citation statements)

References 57 publications

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“…26,28,29 Many papers have images of both fundus and or fluorescein angiography (after IP injection) obtained with commercial and expensive Micron-or Scanning Laser Ophthalmoscope (SLO)-based instruments. [30][31][32][33][34][35] Although, these instruments provide comparable images to our device they cost approximately 10 times more than our system. The Micro-III or IV devices (Phoenix Research Labs) are cornea contact imaging devices with a 508 FOV that generate images of high quality.…”

Section: Comparison With Other Types Of Microscopes Used For Preclinical Gene Therapy Studiesmentioning

confidence: 80%

A Novel, Real-Time, In Vivo Mouse Retinal Imaging System

Butler

Sullivan

2015

Invest. Ophthalmol. Vis. Sci.

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Section: Comparison With Other Types Of Microscopes Used For Preclinical Gene Therapy Studiesmentioning

confidence: 80%

A Novel, Real-Time, In Vivo Mouse Retinal Imaging System

Butler

Sullivan

2015

Invest. Ophthalmol. Vis. Sci.

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“…RPE flat mounts were prepared as described ( Oczos et al, 2014 ). After washing, samples were incubated for 1 hr at RT in blocking solution (see above), followed by overnight incubation at 4°C with primary antibodies: rabbit anti-CRE (see above), rabbit anti-ZO-1 (1:100, 40–2200, Thermo Fisher Scientific), mouse anti-β-cat (1:300, 610153, BD Biosciences, Allschwil, Switzerland) or rabbit anti-IBA-1 (see above).…”

Section: Methodsmentioning

confidence: 99%

Impaired ABCA1/ABCG1-mediated lipid efflux in the mouse retinal pigment epithelium (RPE) leads to retinal degeneration

Storti

Klee

Todorova

et al. 2019

eLife

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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.

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“…The thickness of the outer nuclear layer was measured at indicated distances from the optic nerve head using the Adobe Photoshop CS6 ruler tool (Adobe Systems, Inc., San Jose, CA, USA). RPE flatmounts were prepared and stained as described [ 50 ]. Briefly, eyes were enucleated and incubated in 2% paraformaldehyde for 5 min.…”

Section: Methodsmentioning

confidence: 99%

Hif1a inactivation rescues photoreceptor degeneration induced by a chronic hypoxia-like stress

et al. 2018

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Reduced choroidal blood flow and tissue changes in the ageing human eye impair oxygen delivery to photoreceptors and the retinal pigment epithelium. As a consequence, mild but chronic hypoxia may develop and disturb cell metabolism, function and ultimately survival, potentially contributing to retinal pathologies such as age-related macular degeneration (AMD). Here, we show that several hypoxia-inducible genes were expressed at higher levels in the aged human retina suggesting increased activity of hypoxia-inducible transcription factors (HIFs) during the physiological ageing process. To model chronically elevated HIF activity and investigate ensuing consequences for photoreceptors, we generated mice lacking von Hippel Lindau (VHL) protein in rods. This activated HIF transcription factors and led to a slowly progressing retinal degeneration in the ageing mouse retina. Importantly, this process depended mainly on HIF1 with only a minor contribution of HIF2. A gene therapy approach using AAV-mediated RNA interference through an anti-Hif1a shRNA significantly mitigated the degeneration suggesting a potential intervention strategy that may be applicable to human patients.

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Lack of Paraoxonase 1 Alters Phospholipid Composition, but Not Morphology and Function of the Mouse Retina

Cited by 6 publications

References 57 publications

A Novel, Real-Time, In Vivo Mouse Retinal Imaging System

A Novel, Real-Time, In Vivo Mouse Retinal Imaging System

Impaired ABCA1/ABCG1-mediated lipid efflux in the mouse retinal pigment epithelium (RPE) leads to retinal degeneration

Hif1a inactivation rescues photoreceptor degeneration induced by a chronic hypoxia-like stress

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