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小鼠高脂饮食与布鲁赫膜基底沉积物的激光光化学模型

Murine high-fat diet and laser photochemical model of basal deposits in Bruch membrane.

作者信息

Dithmar S, Sharara N A, Curcio C A, Le N A, Zhang Y, Brown S, Grossniklaus H E

机构信息

L. F. Montgomery Ophthalmic Pathology Laboratory, Emory Eye Center, 1365B Clifton Rd NE, Atlanta, GA 30322, USA.

出版信息

Arch Ophthalmol. 2001 Nov;119(11):1643-9. doi: 10.1001/archopht.119.11.1643.

DOI:10.1001/archopht.119.11.1643
PMID:11709015
Abstract

OBJECTIVE

To examine the histologic, histochemical, and ultrastructural changes in Bruch membrane in mice on a high-fat diet with and without laser photochemical injury.

METHODS

Five groups of C57BL/6 mice were studied. Group 1 included 2-month-old mice on a normal diet; group 2 included 8-month-old mice on a normal diet; group 3 included 8-month-old mice on a high-fat diet; groups 4 and 5 included 8-month-old mice on a normal diet or high-fat diet, respectively, that underwent laser application of one eye with argon blue laser (488 nm). The mice were killed and plasma lipid levels were measured. The eyes were examined by standard electron microscopy, filipin histochemistry for unesterified cholesterol (UC) and esterified cholesterol (EC), and the osmium-tannic acid-phenylenediamine method for preserving extracellular lipid particles.

RESULTS

The plasma cholesterol level was significantly higher in the mice on the high-fat diet than the controls (P<.001). Bruch membrane was thicker in group 2 than group 1 (P =.04) and group 3 had a thicker Bruch membrane than group 2 (P =.003). All eyes in group 3 exhibited accumulation of electron-lucent debris. There was no histochemical and ultrastructural evidence that this material represented accumulated UC or EC. Seven of 9 laser-injured eyes in group 5 accumulated basal laminar deposit (BlamD)-like material in Bruch membrane (P =.02).

CONCLUSIONS

Electron-lucent debris accumulates in murine Bruch membrane, and the amount correlates with age and high-fat diet. This debris has some similarities with basal linear deposits, although the debris does not form a discrete layer external to the basement membrane of the retinal pigment epithelium as occurs in basal linear deposits. These deposits do not appear to be UC or EC. Laser photochemical injury of the retinal pigment epithelium may result in the appearance of BlamD-like deposits in eyes with electron-lucent debris. The BlamD-like deposits in this model are similar to the basal laminar deposits that occur in age-related macular degeneration.

CLINICAL RELEVANCE

This is an animal model of ultrastructural BlamD-like material in Bruch membrane that is very similar to the deposits that occur in age-related macular degeneration.

摘要

目的

研究高脂饮食且伴有或不伴有激光光化学损伤的小鼠布鲁赫膜的组织学、组织化学及超微结构变化。

方法

对五组C57BL/6小鼠进行研究。第1组为2月龄正常饮食小鼠;第2组为8月龄正常饮食小鼠;第3组为8月龄高脂饮食小鼠;第4组和第5组分别为8月龄正常饮食或高脂饮食小鼠,其中一只眼睛接受氩蓝激光(488nm)照射。处死小鼠并测量血浆脂质水平。通过标准电子显微镜、用于游离胆固醇(UC)和酯化胆固醇(EC)的 Filipin 组织化学以及用于保存细胞外脂质颗粒的锇 - 单宁酸 - 苯二胺方法对眼睛进行检查。

结果

高脂饮食小鼠的血浆胆固醇水平显著高于对照组(P<.001)。第2组的布鲁赫膜比第1组厚(P =.04),第3组的布鲁赫膜比第2组厚(P =.003)。第3组所有眼睛均出现电子透亮碎片积聚。没有组织化学和超微结构证据表明该物质代表积聚的UC或EC。第5组9只激光损伤眼中有7只在布鲁赫膜中积聚了类基底膜沉积物(BlamD)样物质(P =.02)。

结论

电子透亮碎片在小鼠布鲁赫膜中积聚,其数量与年龄和高脂饮食相关。尽管这些碎片不像基底线性沉积物那样在视网膜色素上皮基底膜外部形成离散层,但与基底线性沉积物有一些相似之处。这些沉积物似乎不是UC或EC。视网膜色素上皮的激光光化学损伤可能导致在有电子透亮碎片的眼睛中出现类BlamD沉积物。该模型中的类BlamD沉积物类似于年龄相关性黄斑变性中出现的基底膜沉积物。

临床意义

这是一种布鲁赫膜中超微结构类BlamD物质的动物模型,与年龄相关性黄斑变性中出现的沉积物非常相似。

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