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学科主题临床医学
Naloxone Ameliorates Retinal Lesions in Ccl2/Cx3cr1 Double-Deficient Mice via Modulation of Microglia
Shen, Defen1; Cao, Xiaoguang1,3; Zhao, Lian2; Tuo, Jingsheng1; Wong, Wai T.2; Chan, Chi-Chao1
刊名INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
2011-05-01
DOI10.1167/iovs.10-6114
52期:6页:2897-2904
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Ophthalmology
研究领域[WOS]Ophthalmology
关键词[WOS]INDUCED PHOTORECEPTOR DEGENERATION ; MACULAR DEGENERATION ; NITRIC-OXIDE ; NEURODEGENERATIVE DISEASES ; THERAPEUTIC INTERVENTION ; INTRAOCULAR-PRESSURE ; SUBRETINAL MICROGLIA ; ACTIVATED MICROGLIA ; PARKINSONS-DISEASE ; OPIOID RECEPTOR
英文摘要

PURPOSE. The role of naloxone, an opioid receptor antagonist, on microglial inhibition and neuroprotective effects has been reported in lipopolysaccharide (LPS)-induced neurodegeneration and light-induced photoreceptor degeneration. The authors evaluated the effects of naloxone on Ccl2(-/-)/Cx3cr1(-/-) (DKO) mice, a murine model of age-related macular degeneration (AMD).

METHODS. Two-month-old DKO and wild-type controls were given daily intraperitoneal injections of naloxone or PBS for 2 months. Animals were examined monthly by funduscopy. Ocular tissue was analyzed histologically and in retinal flat mount preparations. Ocular A2E was measured using HPLC. Quantitative RT-PCR analyzed TNF-alpha, IL-1 beta, IL-10 and TLR4 transcripts in the DKO eyes and LPS activated culture microglial cells. Serum nitrite was measured using Griess colorimetric reaction.

RESULTS. Naloxone ameliorated the clinical progression and severity of retinal lesions in the DKO mice compared with those of untreated controls. Histopathology also showed less focal retinal degeneration in the treated DKO mice than in controls. The aggregation of microglia in the outer retina in DKO mice was significantly reduced in naloxone-treated animals compared with control untreated DKO. Ocular TNF-alpha, IL-1 beta, and TLR4 transcripts and A2E were significantly lower in naloxone-treated DKO animals and cultured microglial cells than in controls, as were serum nitrite levels.

CONCLUSIONS. Naloxone significantly reduces the progress of retinal lesions in DKO mice. Naloxone modulates microglia accumulation and activation at the site of retinal degeneration, which may be mediated by inhibition of the proinflammatory molecules of NO, TNF-alpha, and IL-beta. The potential therapeutic effects of naloxone on retinal degeneration, including AMD, warrants further investigation. (Invest Ophthalmol Vis Sci. 2011;52:2897-2904) DOI:10.1167/iovs.10-6114

语种英语
WOS记录号WOS:000291100800005
引用统计
被引频次:20[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/52644
专题北京大学第二临床医学院_眼科
作者单位1.NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA
2.NEI, Unit Neuronal & Glial Interact Retinal Dis, NIH, Bethesda, MD 20892 USA
3.Peking Univ, Dept Ophthalmol, Peoples Hosp, Beijing 100871, Peoples R China
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Shen, Defen,Cao, Xiaoguang,Zhao, Lian,et al. Naloxone Ameliorates Retinal Lesions in Ccl2/Cx3cr1 Double-Deficient Mice via Modulation of Microglia[J]. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE,2011,52(6):2897-2904.
APA Shen, Defen,Cao, Xiaoguang,Zhao, Lian,Tuo, Jingsheng,Wong, Wai T.,&Chan, Chi-Chao.(2011).Naloxone Ameliorates Retinal Lesions in Ccl2/Cx3cr1 Double-Deficient Mice via Modulation of Microglia.INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE,52(6),2897-2904.
MLA Shen, Defen,et al."Naloxone Ameliorates Retinal Lesions in Ccl2/Cx3cr1 Double-Deficient Mice via Modulation of Microglia".INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 52.6(2011):2897-2904.
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