Docosahexaenoic acid attenuates microglial activation and delays early retinal degeneration

被引：72

作者：

Ebert, Stefanie ^{[1
]}

Weigelt, Karin ^{[1
]}

Walczak, Yana ^{[1
]}

Drobnik, Wolfgang ^{[2
]}

Mauerer, Richard ^{[2
]}

Hume, David A. ^{[3
,4
]}

Weber, Bernhard H. F. ^{[1
]}

Langmann, Thomas ^{[1
]}

机构：

[1] Univ Regensburg, Inst Human Genet, D-93042 Regensburg, Germany

[2] Med Care Ctr Weiden, Synlab Med Care Serv, Weiden, Germany

[3] Univ Edinburgh, Roslin Inst, Roslin, Midlothian, Scotland

[4] Univ Edinburgh, Royal Dick Sch Vet Studies, Roslin, Midlothian, Scotland

来源：

JOURNAL OF NEUROCHEMISTRY | 2009年 / 110卷 / 06期

基金：

英国医学研究理事会;

关键词：

docosahexaenoic acid; microglia; retina; retinoschisis; RETINOSCHISIN-DEFICIENT RETINA; GENE-THERAPY; NEUROPROTECTIN D1; CELL-SURVIVAL; CANINE MODEL; MOUSE RETINA; LIPID BODIES; FATTY-ACIDS; ROD; RESCUE;

D O I：

10.1111/j.1471-4159.2009.06286.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Microgliosis is a common phenomenon in neurodegenerative disorders including retinal dystrophies. We performed a detailed characterization of activated microglia in the retinoschisin (Rs1h)-deficient (Rs1h(-/Y)) mouse model of inherited retinal degeneration. To visualize and isolate microglia, we crossed Rs1h(-/Y) animals with transgenic MacGreen mice, which express green fluorescent protein under the control of the macrophage-specific csf1r promoter. Activated microglia were detected in retinal sections and whole-mounts of early postnatal MacGreen/Rs1h(-/Y) mice before the onset of overt neuronal cell death. These activated microglia contained prominent lipid droplets and analysis of the retinal lipid composition showed decreased docosahexaenoic acid (DHA) levels in Rs1h(-/Y) retinas. To establish a link between microglia activation, reduced DHA levels, and neurodegeneration, a dietary intervention study was performed. Female Rs1h(-/-) mice and their Rs1h(-/Y) litter were either subjected to a diet enriched with DHA, or a control chow lacking DHA. Supplementation with DHA enhanced photoreceptor survival and converted activated microglia to a quiescent phenotype. Furthermore, DHA, but not docosapentaenoic acid or adrenic acid reduced pro-inflammatory gene expression, migration, and lipid accumulation of cultured BV-2 microglia. We conclude that retinal DHA levels control the activity of microglia and thereby may affect the progression and extent of retinal degeneration.

引用

页码：1863 / 1875

页数：13

共 52 条

[51] Dap12 expression in activated microglia from retinoschisin-deficient retina and its PU.1-dependent promoter regulation [J].

Weigelt, Karin ;

Ernst, Wolfgang ;

Walczak, Yana ;

Ebert, Stefanie ;

Loenhardt, Thomas ;

Klug, Maja ;

Rehli, Michael ;

Weber, Bernhard H. F. ;

Langmann, Thomas .

JOURNAL OF LEUKOCYTE BIOLOGY, 2007, 82 (06) :1564-1574

[52] RS-1 gene delivery to an adult Rs1h knockout mouse model restores ERG b-wave with reversal of the electronegative waveform of X-linked retinoschisis [J].

Zeng, Y ;

Takada, Y ;

Kjellstrom, S ;

Hiriyanna, K ;

Tanikawa, A ;

Wawrousek, E ;

Smaoui, N ;

Caruso, R ;

Bush, RA ;

Sieving, PA .

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2004, 45 (09) :3279-3285

← 1 2 3 4 5 6 →