肾素-血管紧张素-醛固酮系统与早产儿视网膜病变_Chinese Journal of Ocular Fundus Diseases

Authors：

李静 ,  杨赞章 , 李志金

054001 邢台市人民医院儿三科(李静);河北省眼科医院河北省眼科学重点实验室(杨赞章、李志金);

Corresponding author：

杨赞章, Email: yangzanzhang@163.com

Keywords：

肾素-血管紧张素系统/生理学; 早产儿视网膜病/病因学; 综述

DOI：

10.3760/cma.j.issn.1005-1015.2014.01.029

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眼组织中存在着独立于全身的肾素-血管紧张素-醛固酮系统(RAAS),在视网膜新生血管生成、炎症反应和氧化应激等方面发挥着重要作用。目前国内对RAAS在糖尿病视网膜病变中的研究文献较多,但对RAAS在早产儿视网膜病变(ROP)方面的研究却鲜见报道。国外多项研究表明,RAAS在ROP病理过程中也发挥着重要作用,主要体现在促进眼内炎症因子、氧自由基、血管生长因子和新生血管的生成方面。而抑制RAAS中某些成员的活性,显示出一定的抗炎、抗氧化应激、抑制新生血管形成的效应,提示RAAS中的多个成员有望成为防治ROP等增生性眼病的新靶点。进一步探讨RAAS与ROP的关系,将有助于加深对ROP发生发展机制的了解。

Citation： 李静, 杨赞章, 李志金. 肾素-血管紧张素-醛固酮系统与早产儿视网膜病变. Chinese Journal of Ocular Fundus Diseases, 2014, 30(1): 100-103. doi: 10.3760/cma.j.issn.1005-1015.2014.01.029 Copy

1.	Rivera JC, Sapieha P, Joyal JS, et al. Understanding retinopathy of prematurity:update on pathogenesis[J]. Neonatology, 2011, 100:343-353.
2.	Wilkinson-Berka JL, Agrotis A, Deliyanti D. The retinal renin-angiotensin system:roles of angiotensin Ⅱ and aldosterone[J]. Peptides, 2012, 36:142-150.
3.	Carey RM, Padia SH. Angiotensin AT2 receptors:control of renal sodium excretion and blood pressure[J]. Trends Endocrinol Metab, 2008,19:84-87.
4.	Senanayake Pd, Drazba J, Shadrach K, et al. Angiotensin Ⅱ and its receptor subtypes in the human retina[J]. Invest Ophthalmol Vis Sci, 2007, 48:3301-3311.
5.	Ozawa Y, Yuki K, Yamagishi R, et al. Renin-angiotensin system involvement in the oxidative stress-induced neurodegeneration of cultured retinal ganglion cells[J]. Jpn J Ophthalmol, 2013, 57:126-132.
6.	Kanda A, Noda K, Saito W, et al.(Pro)renin receptor is associated with angiogenic activity in proliferative diabetic retinopathy[J]. Diabetologia,2012, 55:3104-3113.
7.	Wilkinson-Berka JL, Miller AG, Fletcher EL. Prorenin and the (pro)renin receptor:do they have a pathogenic role in the retina?[J]. Front Biosci (Elite Ed), 2010, 2:1054-1064.
8.	Deliyanti D, Miller AG, Tan G, et al. Neovascularization is attenuated with aldosterone synthase inhibition in rats with retinopathy[J]. Hypertension, 2012, 59:607-613.
9.	Danser AH, Derkx FH, Admiraal PJ, et al. Angiotensin levels in the eye[J]. Invest Ophthalmol Vis Sci,1994, 35:1008-1018.
10.	Shimizu H, Hirose Y, Goto S, et al. Indoxyl sulfate enhances angiotensin Ⅱ signaling through upregulation of epidermal growth factor receptor expression in vascular smooth muscle cells[J]. Life Sci, 2012, 91:172-177.
11.	Ji Y, Wang Z, Li Z, et al. Angiotensin Ⅱ induces angiogenic factors production partly via AT1/JAK2/STAT3/SOCS3 signaling pathway in MHCC97H cells[J]. Cell Physiol Biochem, 2012, 29:863-874.
12.	Nakamura S, Tsuruma K, Shimazawa M, et al. Candesartan, an angiotensin Ⅱ type 1 receptor antagonist, inhibits pathological retinal neovascularization by downregulating VEGF receptor-2 expression[J]. Eur J Pharmacol, 2012, 685:8-14.
13.	Case AJ, Li S, Basu U, et al. Mitochondrial-localized NADPH oxidase 4 is a source of superoxide in angiotensin Ⅱ-stimulated neurons[J]. Am J Physiol Heart Circ Physiol, 2013,305:19-28.
14.	Ryu S, Shin JS, Cho YW, et al. Fimasartan, anti-hypertension drug, suppressed inducible nitric oxide synthase expressions via nuclear factor-kappa B and activator protein-1 inactivation[J]. Biol Pharm Bull, 2013,36:467-474.
15.	Moravski CJ, Kelly DJ, Cooper ME, et al. Retinal neovascularization is prevented by blockade of the renin-angiotensin system[J]. Hypertension, 2000,36:1099-1104.
16.	Wilkinson-Berka JL, Tan G, Binger KJ, et al. Aliskiren reduces vascular pathology in diabetic retinopathy and oxygen-induced retinopathy in the transgenic (mRen-2)27 rat[J]. Diabetologia, 2011, 54:2724-2735.
17.	Lonchampt M, Pennel L, Duhault J. Hyperoxia/normoxia-driven retinal angiogenesis in mice:a role for angiotensin Ⅱ[J]. Invest Ophthalmol Vis Sci, 2001, 42:429-432.
18.	Hård AL, Wennerholm UB, Niklasson A, et al. Severe ROP in twins after blockage of the renin-angiotensin system during gestation[J]. Acta Paediatr, 2008,97:1142-1144.
19.	Downie LE, Pianta MJ, Vingrys AJ, et al. AT1 receptor inhibition prevents astrocyte degeneration and restores vascular growth in oxygen-induced retinopathy[J]. Glia, 2008, 56:1076-1090.
20.	Fletcher EL, Downie LE, Hatzopoulos K, et al. The significance of neuronal and glial cell changes in the rat retina during oxygen-induced retinopathy[J]. Doc Ophthalmol, 2010, 120:67-86.
21.	Fletcher EL, Phipps JA, Ward MM, et al. The renin-angiotensin system in retinal health and disease:its influence on neurons, glia and the vasculature[J].Prog Retin Eye Res, 2010, 29:284-311.
22.	Sarlos S, Rizkalla B, Moravski CJ,et al. Retinal angiogenesis is mediated by an interaction between the angiotensin type 2 receptor, VEGF, and angiopoietin[J].Am J Pathol,2003,163:879-887.
23.	Huang Y,Wongamorntham S,Kasting J,el al.Renin increases mesangial cell transforming growth factor-beta1 and matrix proteins through receptor-mediated, angiotensin Ⅱ-independent mechanisms[J]. Kidney Int, 2006, 69:105-113.
24.	Alcazar O, Cousins SW, Striker GE, et al. (Pro)renin receptor is expressed in human retinal pigment epithelium and participates in extracellular matrix remodeling[J]. Exp Eye Res, 2009, 89:638-647.
25.	Uraoka M, Ikeda K, Nakagawa Y, et al. Prorenin induces ERK activation in endothelial cells to enhance neovascularization independently of the renin-angiotensin system[J]. Biochem Biophys Res Commun, 2009, 390:1202-1207.
26.	Yokota H, Takamiya A, Nagaoka T, et al. Role of prorenin in the pathogenesis of retinal neovascularization[J]. Hokkaido Igaku Zasshi,2008, 83:159-165.
27.	何疆春, 杨晔, 费宇行. 作用于肾素-血管紧张素系统的药物进展[J]. 心肺血管病杂志,2009, 28:434-437.
28.	Yokota H, Nagaoka T, Mori F, et al. Prorenin levels in retinopathy of prematurity[J]. Am J Ophthalmol, 2007,143:531-533.
29.	Seiberth V, Degenring RF, Schmidt R, et al. Acute retinpathia praematurorum:is plasma prorenin level of prognostic value?[J]. Ophthalmologe,2000,97:688-691.
30.	Liu Y, Hirooka K, Nishiyama A, et al. Activation of the aldosterone/mineralocorticoid receptor system and protective effects of mineralocorticoid receptor antagonism in retinal ischemia-reperfusion injury[J]. Exp Eye Res,2012, 96:116-123.
31.	Wilkinson-Berka JL, Tan G, Jaworski K, et al. Identification of a retinal aldosterone system and the protective effects of mineralocorticoid receptor antagonism on retinal vascular pathology[J]. Circ Res,2009, 104:124-133.
32.	Touyz RM, Callera GE. A new look at the eye:aldosterone and mineralocorticoid receptors as novel targets in retinal vasculopathy[J]. Circ Res,2009,104:9-11.
33.	Bomback AS, Klemmer PJ. The incidence and implications of aldosterone breakthrough[J]. Nat Clin Pract Nephrol, 2007,3:486-492.
34.	Wilkinson-Berka JL, Rana I, Armani R, et al. Reactive oxygen species, Nox and angiotensin Ⅱ in angiogenesis:implications for retinopathy[J]. Clin Sci (Lond),2013, 124:597-615.
35.	Sapieha P, Hamel D, Shao Z, et al. Proliferative retinopathies:angiogenesis that blinds[J]. Int J Biochem Cell Biol, 2010, 42:5-12.

1. Rivera JC, Sapieha P, Joyal JS, et al. Understanding retinopathy of prematurity:update on pathogenesis[J]. Neonatology, 2011, 100:343-353.
2. Wilkinson-Berka JL, Agrotis A, Deliyanti D. The retinal renin-angiotensin system:roles of angiotensin Ⅱ and aldosterone[J]. Peptides, 2012, 36:142-150.
3. Carey RM, Padia SH. Angiotensin AT2 receptors:control of renal sodium excretion and blood pressure[J]. Trends Endocrinol Metab, 2008,19:84-87.
4. Senanayake Pd, Drazba J, Shadrach K, et al. Angiotensin Ⅱ and its receptor subtypes in the human retina[J]. Invest Ophthalmol Vis Sci, 2007, 48:3301-3311.
5. Ozawa Y, Yuki K, Yamagishi R, et al. Renin-angiotensin system involvement in the oxidative stress-induced neurodegeneration of cultured retinal ganglion cells[J]. Jpn J Ophthalmol, 2013, 57:126-132.
6. Kanda A, Noda K, Saito W, et al.(Pro)renin receptor is associated with angiogenic activity in proliferative diabetic retinopathy[J]. Diabetologia,2012, 55:3104-3113.
7. Wilkinson-Berka JL, Miller AG, Fletcher EL. Prorenin and the (pro)renin receptor:do they have a pathogenic role in the retina?[J]. Front Biosci (Elite Ed), 2010, 2:1054-1064.
8. Deliyanti D, Miller AG, Tan G, et al. Neovascularization is attenuated with aldosterone synthase inhibition in rats with retinopathy[J]. Hypertension, 2012, 59:607-613.
9. Danser AH, Derkx FH, Admiraal PJ, et al. Angiotensin levels in the eye[J]. Invest Ophthalmol Vis Sci,1994, 35:1008-1018.
10. Shimizu H, Hirose Y, Goto S, et al. Indoxyl sulfate enhances angiotensin Ⅱ signaling through upregulation of epidermal growth factor receptor expression in vascular smooth muscle cells[J]. Life Sci, 2012, 91:172-177.
11. Ji Y, Wang Z, Li Z, et al. Angiotensin Ⅱ induces angiogenic factors production partly via AT1/JAK2/STAT3/SOCS3 signaling pathway in MHCC97H cells[J]. Cell Physiol Biochem, 2012, 29:863-874.
12. Nakamura S, Tsuruma K, Shimazawa M, et al. Candesartan, an angiotensin Ⅱ type 1 receptor antagonist, inhibits pathological retinal neovascularization by downregulating VEGF receptor-2 expression[J]. Eur J Pharmacol, 2012, 685:8-14.
13. Case AJ, Li S, Basu U, et al. Mitochondrial-localized NADPH oxidase 4 is a source of superoxide in angiotensin Ⅱ-stimulated neurons[J]. Am J Physiol Heart Circ Physiol, 2013,305:19-28.
14. Ryu S, Shin JS, Cho YW, et al. Fimasartan, anti-hypertension drug, suppressed inducible nitric oxide synthase expressions via nuclear factor-kappa B and activator protein-1 inactivation[J]. Biol Pharm Bull, 2013,36:467-474.
15. Moravski CJ, Kelly DJ, Cooper ME, et al. Retinal neovascularization is prevented by blockade of the renin-angiotensin system[J]. Hypertension, 2000,36:1099-1104.
16. Wilkinson-Berka JL, Tan G, Binger KJ, et al. Aliskiren reduces vascular pathology in diabetic retinopathy and oxygen-induced retinopathy in the transgenic (mRen-2)27 rat[J]. Diabetologia, 2011, 54:2724-2735.
17. Lonchampt M, Pennel L, Duhault J. Hyperoxia/normoxia-driven retinal angiogenesis in mice:a role for angiotensin Ⅱ[J]. Invest Ophthalmol Vis Sci, 2001, 42:429-432.
18. Hård AL, Wennerholm UB, Niklasson A, et al. Severe ROP in twins after blockage of the renin-angiotensin system during gestation[J]. Acta Paediatr, 2008,97:1142-1144.
19. Downie LE, Pianta MJ, Vingrys AJ, et al. AT1 receptor inhibition prevents astrocyte degeneration and restores vascular growth in oxygen-induced retinopathy[J]. Glia, 2008, 56:1076-1090.
20. Fletcher EL, Downie LE, Hatzopoulos K, et al. The significance of neuronal and glial cell changes in the rat retina during oxygen-induced retinopathy[J]. Doc Ophthalmol, 2010, 120:67-86.
21. Fletcher EL, Phipps JA, Ward MM, et al. The renin-angiotensin system in retinal health and disease:its influence on neurons, glia and the vasculature[J].Prog Retin Eye Res, 2010, 29:284-311.
22. Sarlos S, Rizkalla B, Moravski CJ,et al. Retinal angiogenesis is mediated by an interaction between the angiotensin type 2 receptor, VEGF, and angiopoietin[J].Am J Pathol,2003,163:879-887.
23. Huang Y,Wongamorntham S,Kasting J,el al.Renin increases mesangial cell transforming growth factor-beta1 and matrix proteins through receptor-mediated, angiotensin Ⅱ-independent mechanisms[J]. Kidney Int, 2006, 69:105-113.
24. Alcazar O, Cousins SW, Striker GE, et al. (Pro)renin receptor is expressed in human retinal pigment epithelium and participates in extracellular matrix remodeling[J]. Exp Eye Res, 2009, 89:638-647.
25. Uraoka M, Ikeda K, Nakagawa Y, et al. Prorenin induces ERK activation in endothelial cells to enhance neovascularization independently of the renin-angiotensin system[J]. Biochem Biophys Res Commun, 2009, 390:1202-1207.
26. Yokota H, Takamiya A, Nagaoka T, et al. Role of prorenin in the pathogenesis of retinal neovascularization[J]. Hokkaido Igaku Zasshi,2008, 83:159-165.
27. 何疆春, 杨晔, 费宇行. 作用于肾素-血管紧张素系统的药物进展[J]. 心肺血管病杂志,2009, 28:434-437.
28. Yokota H, Nagaoka T, Mori F, et al. Prorenin levels in retinopathy of prematurity[J]. Am J Ophthalmol, 2007,143:531-533.
29. Seiberth V, Degenring RF, Schmidt R, et al. Acute retinpathia praematurorum:is plasma prorenin level of prognostic value?[J]. Ophthalmologe,2000,97:688-691.
30. Liu Y, Hirooka K, Nishiyama A, et al. Activation of the aldosterone/mineralocorticoid receptor system and protective effects of mineralocorticoid receptor antagonism in retinal ischemia-reperfusion injury[J]. Exp Eye Res,2012, 96:116-123.
31. Wilkinson-Berka JL, Tan G, Jaworski K, et al. Identification of a retinal aldosterone system and the protective effects of mineralocorticoid receptor antagonism on retinal vascular pathology[J]. Circ Res,2009, 104:124-133.
32. Touyz RM, Callera GE. A new look at the eye:aldosterone and mineralocorticoid receptors as novel targets in retinal vasculopathy[J]. Circ Res,2009,104:9-11.
33. Bomback AS, Klemmer PJ. The incidence and implications of aldosterone breakthrough[J]. Nat Clin Pract Nephrol, 2007,3:486-492.
34. Wilkinson-Berka JL, Rana I, Armani R, et al. Reactive oxygen species, Nox and angiotensin Ⅱ in angiogenesis:implications for retinopathy[J]. Clin Sci (Lond),2013, 124:597-615.
35. Sapieha P, Hamel D, Shao Z, et al. Proliferative retinopathies:angiogenesis that blinds[J]. Int J Biochem Cell Biol, 2010, 42:5-12.

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Chinese Journal of Ocular Fundus Diseases

肾素-血管紧张素-醛固酮系统与早产儿视网膜病变

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