High density lipoprotein mediated lipid efflux from retinal pigment epithelial cells in culture.

Cardiovascular Research Institute, University of California, San Francisco, 94143, USA.
British Journal of Ophthalmology (Impact Factor: 2.81). 06/2006; 90(5):616-20. DOI: 10.1136/bjo.2005.085076
Source: PubMed

ABSTRACT [corrected] The transport of radiolabelled photoreceptor outer segments (POS) lipids was investigated by cultured retinal pigment epithelial cells (RPE). Phagocytosis of POS by the RPE is essential to maintain the health and function of the photoreceptors in vivo. POS are phagocytised at the apical cell surface of RPE cells. Phagocytised POS lipids may be either recycled to the photoreceptors for reincorporation into new POS or they may be transported to the basolateral surface for efflux into the circulation.
The authors have demonstrated that high density lipoprotein (HDL) stimulates efflux of radiolabelled lipids, of POS origin, from the basal surface of RPE cells in culture. Effluxed lipids bind preferentially to HDL species of low and high molecular weight. Effluxed radiolabelled phosphotidyl choline was the major phospholipid bound to HDL, with lesser amounts of phosphatidyl ethanolamine, phosphatidyl inosotol. Effluxed radiolabelled triglycerides, cholesterol, and cholesterol esters also bound to HDL. Lipid free apolipoprotein A-I (apoA-I) and apoA-I containing vesicles also stimulate lipid efflux.
The findings suggest a role for HDL and apoA-I in regulating lipid and cholesterol transport from RPE cells that may influence the pathological lipid accumulation associated with age related macular degeneration.

  • [Show abstract] [Hide abstract]
    ABSTRACT: By integrating the thermomechanically coupled simulation with the mathematically modeling of microstructure evolution using Finite Element Method (FEM), the study of the dynamic recrystallization (DRX) of Ti–6.5Al–3.5Mo–1.5Zr–0.3Si alloy in β-forging process is conducted. Through physical experiment, microstructure characterization and FEM-based microstructure modeling, the DRX behavior of the Ti-alloy in β-forging process is extensively explored. The effects of plastic deformation strain, strain rate and deformation temperature on the DRX of the Ti-alloy in terms of DRX volume fraction, DRX grain size and the average grain size are systematically investigated. The simulation results show that the increase of plastic deformation strain, deformation temperature, and strain rate contributes to the DRX of the alloy. The simulation and experimental results further reveal that the FEM-based microstructure evolution modeling is able to predict the DRX behavior and the microstructure evolution of Ti–6.5Al–3.5Mo–1.5Zr–0.3Si alloy in β-forging process.
    Materials and Design 03/2011; 32(3):1283-1291. DOI:10.1016/j.matdes.2010.09.033 · 3.17 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: Biochemical and genetic analyses established a contribution of lipid metabolism to AMD pathology. PON1 (Paraoxonase 1) encodes an anti-oxidative protein involved in high density lipoprotein (HDL) function and was found to be associated with AMD. Here we used Pon1-/- mice to study the influence of PON1 on retinal physiology and to reveal the potential impact of PON1 on AMD aetiology. Methods: Laser capture microdissection served to isolate single retinal layers. Retinal function was assessed by ERG. Retinal and RPE morphology were monitored by fundus imaging, fluorescein angiography, light and transmission electron microscopy, and immunofluorescence microscopy. Levels of mRNA and composition of phospholipid species were determined by real-time PCR and LC-MS, respectively. Results: Adult (8 weeks old) Pon1-/- mice displayed normal retinal function and morphology, but their retinas contained reduced amounts of lysophosphatidylcholines (LPCs) compared to controls. Aged (12 months old) Pon1-/- animals did not show any morphological or molecular signs of photoreceptor or RPE degeneration, or of accelerated aging. Photoreceptors of Pon1-/- and control mice were similarly susceptible to light damage. Conclusions: PON1 is not essential for normal development, function, ageing and the defense against light damage of the mouse retina. Reduced levels of LPCs in eyes of Pon1-/- mice may reflect a decreased activity of phospholipase A2 or altered anti-oxidative activity in aged eyes.
    Investigative Ophthalmology &amp Visual Science 07/2014; 55(8). DOI:10.1167/iovs.14-14332 · 3.66 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: L’effet des fibrates sur la réduction des événements cardiovasculaires au cours du diabète de type 2 n’avait pu que partiellement être exploré à partir de sous-groupes de patients diabétiques issus des études VAHIT avec le gemfibrozil et BIP avec le bézafibrate. L’étude FIELD ( Fenofibrate intervention and endpoint lowering in diabetes) avec le fénofibrate était la première étude de prévention cardiovasculaire menée dans une large population de sujets diabétiques de type 2. Les résultats de cette étude ont été décevants et l’étude FIELD n’a pas permis de montrer avec force l’efficacité du fénofibrate sur la diminution des événements cardiovasculaires, au cours du diabète de type 2. En effet, le traitement par fénofibrate a entrainé une diminution non significative de 11 % des décès d’origine coronarienne et des infarctus du myocarde non mortels. En outre, le fénofibrate n’a eu aucun effet chez les patients en prévention secondaire. Ces résultats « déconcertants » ont fait germer plusieurs questions. En particulier, l’augmentation significative de l’homocystéine observée chez les patients sous fénofibrate pourrait rendre compte, en partie, de l’effet modeste du fénofibrate sur la réduction du risque cardiovasculaire observé dans FIELD et sur l’augmentation du risque d’accidents thromboemboliques veineux chez les patients sous traitement actif. Les résultats « très mitigés » de l’étude FIELD ne permettent pas de détrôner les statines comme traitement de première intention chez le patient diabétique de type 2. La question qui se pose réellement est de savoir si le fénofibrate en association avec les statines serait susceptible d’apporter un bénéfice supplémentaire en terme de réduction du risque cardiovasculaire. Cette question trouvera sa réponse dans les résultats de l’étude ACCORD actuellement en cours, étudiant l’effet de l’association fénofibrate + simvastatine.
    Médecine des Maladies Métaboliques 01/2008; 2(1). DOI:10.1016/S1957-2557(08)70007-5


Available from