Sirtuin1 over-expression does not impact retinal vascular and neuronal degeneration in a mouse model of oxygen-induced retinopathy.
Sirtuin1 over-expression does not impact retinal vascular and neuronal degeneration in a mouse model of oxygen-induced retinopathy.
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DOI：
10.1371/journal.pone.0085031
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Michan S;Juan AM;Hurst CG;Cui Z;Evans LP;Hatton CJ;Pei DT;Ju M;Sinclair DA;Smith LE;Chen J
增殖性视网膜病变是导致失明的主要原因，包括儿童早产儿视网膜病变（ROP）和成人糖尿病视网膜病变。视网膜病变的特点是初始阶段血管丧失，导致组织缺血和缺氧，第二阶段出现威胁视力的病理性新生血管。先前，我们发现Sirtuin1 (Sirt1)，一种代谢依赖的蛋白去乙酰化酶，在氧诱导的增生性视网膜病变（OIR）小鼠模型中调节血管再生，因为视网膜中Sirt1的神经元耗尽会加重视网膜病变。在这项研究中，我们通过将Sirt1过表达的flox小鼠分别与nesting - cre小鼠或Tie2-Cre小鼠杂交，评估了Sirtuin1在视网膜神经元和血管中的过表达是否可以预防视网膜病变。我们发现，在Nestin表达的视网膜神经元中，Sirt1的过表达不会影响OIR中的血管闭塞或病理性新生血管形成，也不会影响OIR中的神经元变性。同样，在表达血管内皮细胞和单核/巨噬细胞的Tie2中Sirt1的表达增加并不能保护视网膜血管。除了遗传方法外，还将含有Sirt1激活剂白藜芦醇或SRT1720的膳食补充剂喂给患有OIR的野生型小鼠。两种治疗在视网膜病变中均未显示出明显的血管保护作用。综上所述，这些结果表明，尽管内源性Sirt1在视网膜病变中作为应激诱导的保护因子是重要的，但在小鼠中，Sirt1的过表达或小分子激活剂在研究剂量下的治疗并不能提供额外的视网膜病变保护。需要进一步的研究来深入研究Sirt1水平的升高是否可以作为治疗或预防视网膜病变的潜在治疗方法。
Proliferative retinopathy is a leading cause of blindness, including retinopathy of prematurity (ROP) in children and diabetic retinopathy in adults. Retinopathy is characterized by an initial phase of vessel loss, leading to tissue ischemia and hypoxia, followed by sight threatening pathologic neovascularization in the second phase. Previously we found that Sirtuin1 (Sirt1), a metabolically dependent protein deacetylase, regulates vascular regeneration in a mouse model of oxygen-induced proliferative retinopathy (OIR), as neuronal depletion of Sirt1 in retina worsens retinopathy. In this study we assessed whether over-expression of Sirtuin1 in retinal neurons and vessels achieved by crossing Sirt1 over-expressing flox mice with Nestin-Cre mice or Tie2-Cre mice, respectively, may protect against retinopathy. We found that over-expression of Sirt1 in Nestin expressing retinal neurons does not impact vaso-obliteration or pathologic neovascularization in OIR, nor does it influence neuronal degeneration in OIR. Similarly, increased expression of Sirt1 in Tie2 expressing vascular endothelial cells and monocytes/macrophages does not protect retinal vessels in OIR. In addition to the genetic approaches, dietary supplement with Sirt1 activators, resveratrol or SRT1720, were fed to wild type mice with OIR. Neither treatment showed significant vaso-protective effects in retinopathy. Together these results indicate that although endogenous Sirt1 is important as a stress-induced protector in retinopathy, over-expression of Sirt1 or treatment with small molecule activators at the examined doses do not provide additional protection against retinopathy in mice. Further studies are needed to examine in depth whether increasing levels of Sirt1 may serve as a potential therapeutic approach to treat or prevent retinopathy.
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DOI：
10.1126/science.1231097
发表时间：
2013-03-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hubbard BP;Gomes AP;Dai H;Li J;Case AW;Considine T;Riera TV;Lee JE;E SY;Lamming DW;Pentelute BL;Schuman ER;Stevens LA;Ling AJ;Armour SM;Michan S;Zhao H;Jiang Y;Sweitzer SM;Blum CA;Disch JS;Ng PY;Howitz KT;Rolo AP;Hamuro Y;Moss J;Perni RB;Ellis JL;Vlasuk GP;Sinclair DA
通讯作者：
Sinclair DA
影响因子：
64.8
作者：
Guarani V;Deflorian G;Franco CA;Krüger M;Phng LK;Bentley K;Toussaint L;Dequiedt F;Mostoslavsky R;Schmidt MHH;Zimmermann B;Brandes RP;Mione M;Westphal CH;Braun T;Zeiher AM;Gerhardt H;Dimmeler S;Potente M
通讯作者：
Potente M
DOI：
10.1016/j.bbapap.2009.10.025
发表时间：
2010-08
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Baur JA
通讯作者：
Baur JA
当前有关早产视网膜病变的更新：筛查和治疗。
影响因子：
3.6
作者：
Chen J;Stahl A;Hellstrom A;Smith LE
通讯作者：
Smith LE
影响因子：
9.8
作者：
Chen, Jing;Smith, Lois E. H.
通讯作者：
Smith, Lois E. H.