Open AccessJournal Article
In Vivo Consequences Of Cholesterol-24s-hydroxylase (CYP46A1) Inhibition By Voriconazole On Cholesterol Homeostasis And Function In The Rat Retina
Cynthia Fourgeux,Lucy Martine,B. Pasquis,Niyazi Acar,Alain M. Bron,Catherine P. Creuzot Garcher,Lionel Bretillon +6 more
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In this article, the consequences of voriconazole on cholesterol homeostasis and function in the retina were evaluated in rats with daily intraperitoneal injections of VORICONAZOLA (60 mg/kg), minocycline (22mg/kg) or vehicle during five consecutive days.Abstract:
Cholesterol 24S-hydroxylase (CYP46A1) converts cholesterol into 24S-hydroxycholesterol in neurons and participates in cholesterol homeostasis in the central nervous system, including the retina. We aimed to evaluate the consequences of CYP46A1 inhibition by voriconazole on cholesterol homeostasis and function in the retina. Rats received daily intraperitoneal injections of voriconazole (60mg/kg), minocycline (22mg/kg), voriconazole plus minocycline, or vehicle during five consecutive days. The rats were submitted to electroretinography to monitor retinal functionality. Cholesterol and 24S-hydroxycholesterol were measured in plasma, brain and retina by gas chromatography-mass spectrometry. The expression of CYP46A1, and GFAP as a marker for glial activation was analyzed in the retina and brain. Cytokines and chemokines were measured in plasma, vitreous, retina and brain. Voriconazole significantly impaired the functioning of the retina as exemplified by the reduced amplitude and increased latency of the b-wave of the electroretinogram, and altered oscillary potentials. Voriconazole decreased 24S-hydroxycholesterol levels in the retina. Unexpectedly, CYP46A1 and GFAP expression was increased in the retina of voriconazole-treated rats. ICAM-1 and MCP-1 showed significant increases in the retina and vitreous body. Minocycline did not reverse the effects of voriconazole. Our data highlighted the cross talk between retinal ganglion cells and glial cells in the retina, suggesting that reduced 24S-hydroxycholesterol concentration in the retina may be detected by glial cells, which were consequently activated.read more
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Dissertation
Rôle des acides gras polyinsaturés alimentaires dans l'homéostasie lipidique de la rétine en conditions physiologiques et pathologiques liées au vieillissement
TL;DR: In this paper, the authors evaluated the effect of a diet enriched with AGPI-LC omega-3 on the risk of developing the retinopathie diabetique (RD) and T2D.
Dissertation
Cholestérol-24S-hydroxylase (CYP46A1) et homéostasie du cholestérol dans la rétine en conditions physiologiques et pathologiques
TL;DR: Fourgeux et al. as mentioned in this paper evaluated le role of cholesterol-24S-hydroxylase dans the retine in conditions physiologiques and pathologiques, and showed that it has a role potentiel dans certain pathologies comme maladie d'Alzheimer.
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Minocycline Reduces Proinflammatory Cytokine Expression, Microglial Activation, and Caspase-3 Activation in a Rodent Model of Diabetic Retinopathy
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Importance of a novel oxidative mechanism for elimination of brain cholesterol. Turnover of cholesterol and 24(S)-hydroxycholesterol in rat brain as measured with 18O2 techniques in vivo and in vitro.
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