Decanini Alejandra, Nordgaard Curtis L, Feng Xiao, Ferrington Deborah A, Olsen Timothy W
Department of Ophthalmology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Am J Ophthalmol. 2007 Apr;143(4):607-15. doi: 10.1016/j.ajo.2006.12.006. Epub 2007 Feb 5.
To examine changes of select reduction-oxidation (redox) sensitive proteins from human donor retinal pigment epithelium (RPE) at four stages of age-related macular degeneration (AMD).
Experimental study.
Human donor eyes were obtained from the Minnesota Lions Eye Bank and graded using the Minnesota Grading System (MGS) into four stages that correspond to stages defined by the age-related eye disease study (AREDS). Protein content in RPE homogenates was measured using Western immunoblotting with protein-specific antibodies.
The content of several antioxidant enzymes and specific proteins that facilitate refolding or degradation of oxidatively damaged proteins increased significantly in MGS stage 3. These proteins are involved in the primary (copper-zinc superoxide dismutase [CuZnSOD], manganese superoxide dismutase [MnSOD], and catalase) and secondary (heat shock protein [HSP] 27, HSP 90, and proteasome) defense against oxidative damage. Additionally, the insulin pro-survival receptor exhibited disease-related upregulation.
The pattern of protein changes identified in human donor tissue graded using the MGS support the role of oxidative mechanisms in the pathogenesis and progression of AMD. The MGS uses nearly identical clinical definitions and grading criteria of AMD that are used in the AREDS, so our results apply to clinical and epidemiologic studies using similar definitions. Results from our protein analysis of human donor tissue helps to explain altered oxidative stress regulation and cell-survival pathways that occur in progressive stages of AMD.
研究在年龄相关性黄斑变性（AMD）的四个阶段中，人类供体视网膜色素上皮（RPE）中选定的氧化还原敏感蛋白的变化。
实验研究。
从明尼苏达狮子眼库获取人类供体眼，并使用明尼苏达分级系统（MGS）将其分级为四个阶段，这四个阶段与年龄相关性眼病研究（AREDS）定义的阶段相对应。使用针对特定蛋白质的抗体通过蛋白质免疫印迹法测量RPE匀浆中的蛋白质含量。
在MGS 3期，几种抗氧化酶以及促进氧化损伤蛋白质重折叠或降解的特定蛋白质的含量显著增加。这些蛋白质参与对氧化损伤的一级防御（铜锌超氧化物歧化酶[CuZnSOD]、锰超氧化物歧化酶[MnSOD]和过氧化氢酶）和二级防御（热休克蛋白[HSP]27、HSP 90和蛋白酶体）。此外，胰岛素促生存受体表现出与疾病相关的上调。
使用MGS分级的人类供体组织中确定的蛋白质变化模式支持氧化机制在AMD发病机制和进展中的作用。MGS使用与AREDS中几乎相同的AMD临床定义和分级标准，因此我们的结果适用于使用类似定义的临床和流行病学研究。我们对人类供体组织的蛋白质分析结果有助于解释AMD进展阶段中氧化应激调节和细胞生存途径的改变。
