Deletion of Efemp1 Is Protective Against the Development of Sub-RPE Deposits in Mouse Eyes.
Deletion of Efemp1 Is Protective Against the Development of Sub-RPE Deposits in Mouse Eyes.
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DOI：
10.1167/iovs.16-20955
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发表时间：
2017-03-01
影响因子：
4.4
通讯作者：
Marmorstein LY
中科院分区：
文献类型：
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作者：
Stanton JB;Marmorstein AD;Zhang Y;Marmorstein LY
EFEMP 1（纤蛋白-3）在Malattia Leventinese/Doyne蜂窝状视网膜营养不良（ML/DHRD）中发生突变，这是一种类似于AMD的遗传性黄斑营养不良。ML/DHRD和AMD两者的特征在于存在亚RPE沉积物。Efemp 1基因敲除小鼠不产生亚RPE沉积物。这项研究是为了测试是否可以通过实验施加的应激条件，导致野生型小鼠发展亚RPE沉积物诱导Efemp 1基因敲除小鼠的亚RPE沉积物。在6、18或24个月大的Efemp 1基因敲除小鼠和对照小鼠喂食合成高脂饮食（HFD）。开始HFD后1个月开始，一组小鼠每天暴露于香烟烟雾中1个月，另一组小鼠每隔一天接受488 nm氩激光的光化学损伤2周。治疗后，进行组织学分析以评估是否诱导了RPE下沉积物。基底层沉积物（BLamD），一种形式的亚RPE沉积物，在18个月和24个月大的野生型小鼠中观察到，但在暴露于HFD和香烟烟雾或激光损伤后的任何年龄组中的Efemp 1基因敲除小鼠中均未观察到。缺乏fibulin-3的小鼠不产生RPE下沉积物。已知在野生型小鼠中导致BlamD形成的环境氧化应激物（HFD/香烟烟雾或HFD/激光）未能在Efemp 1敲除小鼠中诱导BlamD形成。这些结果表明，纤蛋白-3在BlamD的发展中是一个重要的参与者，并且纤蛋白-3的缺失对BlamD的发展具有保护作用。
EFEMP1 (fibulin-3) is mutated in Malattia Leventinese/Doyne's honeycomb retinal dystrophy (ML/DHRD), an inherited macular dystrophy similar to AMD. Both ML/DHRD and AMD are characterized by the presence of sub-RPE deposits. Efemp1 knockout mice do not develop sub-RPE deposits. This study was to test whether sub-RPE deposits can be induced in Efemp1 knockout mice by experimentally applied stress conditions that cause wild-type mice to develop sub-RPE deposits. Efemp1 knockout and control mice at 6, 18, or 24 months old were fed with a synthetic high-fat diet (HFD). Beginning 1 month after starting the HFD, one group of mice was exposed to cigarette smoke daily for 1 month, and another group of mice was subjected to photochemical injury every other day for 2 weeks from a 488-nm argon laser. After the treatments, histologic analysis was performed to assess whether sub-RPE deposits were induced. Basal laminar deposits (BLamDs), a form of sub-RPE deposits, were observed in the 18- and 24-month-old wild-type mice but not in Efemp1 knockout mice in any age groups after exposure to HFD and cigarette smoke or laser injury. Mice lacking fibulin-3 do not develop sub-RPE deposits. Environmental oxidative stressors (HFD/cigarette smoke or HFD/laser) known to cause BLamD formation in wild-type mice failed to induce BLamD formation in Efemp1 knockout mice. These results suggest that fibulin-3 is a central player in the development of BLamD, and deletion of fibulin-3 is protective against the development of BLamD.