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晚期高强度周期性光诱导视网膜变性大鼠脉络膜新生血管的发展

Development of choroidal neovascularization in rats with advanced intense cyclic light-induced retinal degeneration.

作者信息

Albert Daniel M, Neekhra Aneesh, Wang Shoujian, Darjatmoko Soesiawati R, Sorenson Christine M, Dubielzig Richard R, Sheibani Nader

机构信息

Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave, K6/458 CSC, Madison, WI 53792-4673, USA.

出版信息

Arch Ophthalmol. 2010 Feb;128(2):212-22. doi: 10.1001/archophthalmol.2009.395.

Abstract

OBJECTIVES

To study the progressive changes of intense cyclic light-induced retinal degeneration and to determine whether it results in choroidal neovascularization (CNV).

METHODS

Albino rats were exposed to 12 hours of 3000-lux cyclic light for 1, 3, or 6 months. Fundus examination, fundus photography, fluorescein and indocyanine green angiography, and optical coherence tomography were performed prior to euthanization. Light-exposed animals were euthanized after 1, 3, or 6 months for histopathological evaluation. Retinas were examined for the presence of 4-hydroxy-2-nonenal- and nitrotyrosine-modified proteins by immunofluorescence staining.

RESULTS

Long-term intense cyclic light exposure resulted in retinal degeneration with loss of the outer segments of photoreceptors and approximately two-thirds of the outer nuclear layer as well as development of subretinal pigment epithelium neovascularization after 1 month. Almost the entire outer nuclear layer was absent with the presence of CNV, which penetrated the Bruch membrane and extended into the outer retina after 3 months. Absence of the outer nuclear layer, multiple foci of CNV, retinal pigment epithelial fibrous metaplasia, and connective tissue bands containing blood vessels extending into the retina were observed after 6 months. All intense light-exposed animals showed an increased presence of 4-hydroxy-2-nonenal and nitrotyrosine staining. Optical coherence tomographic and angiographic studies confirmed retinal thinning and leakiness of the newly formed blood vessels.

CONCLUSIONS

Our results suggest that albino rats develop progressive stages of retinal degeneration and CNV after long-term intense cyclic light exposure, allowing the detailed study of the pathogenesis and treatment of age-related macular degeneration.

CLINICAL RELEVANCE

The ability to study the progressive pathogenesis of age-related macular degeneration and CNV will provide detailed knowledge about the disease and aid in the development of target-specific therapy.

摘要

目的

研究高强度周期性光诱导视网膜变性的渐进性变化,并确定其是否会导致脉络膜新生血管(CNV)形成。

方法

将白化大鼠暴露于3000勒克斯的周期性光下12小时,持续1、3或6个月。在安乐死之前进行眼底检查、眼底照相、荧光素和吲哚菁绿血管造影以及光学相干断层扫描。暴露于光下的动物在1、3或6个月后进行安乐死以进行组织病理学评估。通过免疫荧光染色检查视网膜中4-羟基-2-壬烯醛和硝基酪氨酸修饰蛋白的存在情况。

结果

长期高强度周期性光暴露导致视网膜变性,光感受器外段和大约三分之二的外核层丧失,并且在1个月后出现视网膜色素上皮下新生血管形成。3个月后,几乎整个外核层缺失,伴有CNV,其穿透布鲁赫膜并延伸至视网膜外层。6个月后,观察到外核层缺失、多个CNV病灶、视网膜色素上皮纤维化生以及含有延伸至视网膜的血管的结缔组织带。所有暴露于强光的动物均显示4-羟基-2-壬烯醛和硝基酪氨酸染色增加。光学相干断层扫描和血管造影研究证实了视网膜变薄和新形成血管的渗漏。

结论

我们的结果表明,白化大鼠在长期高强度周期性光暴露后会发展为视网膜变性和CNV的渐进阶段,这有助于详细研究年龄相关性黄斑变性的发病机制和治疗方法。

临床意义

研究年龄相关性黄斑变性和CNV渐进性发病机制的能力将提供有关该疾病的详细知识,并有助于开发靶向特异性治疗方法。

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