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Japanese Journal of Ophthalmology

Published in:

01-07-2018 | Laboratory Investigation

Gene expression changes in the retina after systemic administration of aldosterone

Authors: Aoi Ono, Kazuyuki Hirooka, Yuki Nakano, Eri Nitta, Akira Nishiyama, Akitaka Tsujikawa

Published in: Japanese Journal of Ophthalmology | Issue 4/2018

Abstract

Purpose

Retinal ganglion cell (RGC) loss associated with thinning of the retinal nerve fiber layer without elevated intraocular pressure (IOP) occurs after the systemic administration of aldosterone. Since it is important to determine the mechanism of cell death independent of the IOP, we examined gene expression changes in the retina after the systemic administration of aldosterone.

Methods

Following subcutaneous implantation of an osmotic minipump into the mid-scapular region of rats, we administered an 80 μg/kg/day dose of aldosterone. Differences in the gene expression in the retina between normal rats and aldosterone-treated rats were investigated using microarrays. Real-time PCR was used to confirm the differential expression.

Results

Analysis of the microarray data sets revealed the upregulation of 24 genes and the downregulation of 24 genes of key apoptosis-specific genes. Real-time PCR revealed 4 genes (Cdkn1a, Tbox5, Pf4, Vdr) were upregulated while 12 genes (Acvr1c, Asns, Bard1, Card9, Crh, Fcgr1a, Inhba, Kcnh8, Lck, Phlda1, Ptprc, Sh3rf1) were downregulated.

Conclusions

Significant increases and decreases were noted in several genes after the systemic administration of aldosterone. Further studies will need to be undertaken in order to definitively clarify the role of these genes in the eyes of animals with normal-tension glaucoma.

Levene RZ. Low tension glaucoma: a critical review and new material. Surv Ophthalmol. 1980;24:621–64.CrossRefPubMed

Quigley HA. Open-angle glaucoma. N Engl J Med. 1993;328:1097–106.CrossRefPubMed

Cartwright MJ, Anderson DR. Correlation of asymmetric damage with asymmetric intraocular pressure in normal-tension glaucoma (low-tension glaucoma). Arch Ophthalmol. 1988;106:898–900.CrossRefPubMed

Crichton A, Drance SM, Douglas GR, Schulzer M. Unequal intraocular pressure and its relation to asymmetric visual field defects in low-tension glaucoma. Ophthalmology. 1989;96:1312–4.CrossRefPubMed

Abedin S, Simmons RJ, Grant WM. Progressive low-tension glaucoma: treatment to stop glaucomatous cupping and field loss when these progress despite normal intraocular pressure. Ophthalmology. 1982;89:1–6.CrossRefPubMed

de Jong N, Greve EL, Hoyng PF, Geijssen HC. Results of a filtering procedure in low tension glaucoma. Int Ophthalmol. 1989;13:131–8.CrossRefPubMed

Oie S, Ishida K, Yamamoto T. Impact of intraocular pressure reduction on visual field progression in normal-tension glaucoma followed up over 15 years. Jpn J Ophthalmol. 2017. https://doi.org/10.1007/s10384-017-0519-8.PubMedCrossRef

Tezel G, Siegmund KD, Trinkaus K, Trinkaus K, Wax MB, Kass MA, et al. Clinical factors associated with progression of glaucomatous optic disc damage in treated patients. Arch Ophthalmol. 2001;119:813–8.CrossRefPubMed

Flammer J, Haefliger IO, Orgul S, Resink T. Vascular dysregulation: a principal risk factor for glaucomatous damage? J Glaucoma. 1999;8:212–9.CrossRefPubMed

10.

Takebayashi K, Matsumoto S, Aso Y, Inukai T. Aldosterone blockade attenuates urinary monocyte chemoattractant protein-1 and oxidative stress in patients with type 2 diabetes complicated by diabetic nephropathy. J Clin Endocrinol Metab. 2006;91:2214–7.CrossRefPubMed

11.

Shibata S, Nagase M, Yoshida S, Kawachi H, Fujita T. Podocyte as the target for aldosterone: roles of oxidative stress and Sgk1. Hypertension. 2007;49:355–64.CrossRefPubMed

12.

Rossi GP, Sachetto A, Visentin P, Canali C, Graniero GR, Palatini P, et al. Changes in left ventricular anatomy and function in hypertension and primary aldosteronism. Hypertension. 1996;27:1039–45.CrossRefPubMed

13.

Halimi J-M, Mimran A. Albuminuria in untreated patients with primary aldosteronism or essential hypertension. J Hypertens. 1995;13:1801–2.PubMed

14.

Takeda R, Matsubara T, Miyamori I, Hatakeyama H, Morise T. Vascular complications in patients with aldosterone producing adenoma in Japan: comparative study with essential hypertension. The Research Committee of Disorders of Adrenal Hormons in Japan. J Endocrinol Invest. 1995;18:370–3.CrossRefPubMed

15.

Nishimura M, Uzu T, Fujii T, Kuroda S, Nakamura S, Inenega T, et al. Cardiovascular complications in patients with primary aldosteronism. Am J Kidney Dis. 1999;33:261–6.CrossRefPubMed

16.

Fukuda K, Hirooka K, Mizote M, Nakamura T, Itano T, Shiraga F. Neuroprotection against retinal ischemia-reperfusion injury by blocking the angiotensin II type 1 receptor. Invest Ophthalmol Vis Sci. 2010;51:3629–38.CrossRefPubMed

17.

Fujita T, Hirooka K, Nakamura T, Itano T, Nishiyama A, Nagai Y, et al. Neuroprotective effects of angiotensin II type 1 receptor (AT1-R) blocker via modulating AT1-R signaling and decreased extracellular glutamate levels. Invest Ophthalmol Vis Sci. 2012;53:4099–110.CrossRefPubMed

18.

Liu Y, Hirooka K, Nishiyama A, Lei B, Nakamura T, Itano T, et al. Activation of the aldosterone/mineralocorticoid receptor system and protective effects of mineralocorticoid receptor antagonism in retinal ischemia-reperfusion injury. Exp Eye Res. 2012;96:116–23.CrossRefPubMed

19.

Wilkinson-Berka JL, Tan G, Jaworski K, Miller AG. Identification of a retinal aldosterone system and the protective effects of mineralocorticoid receptor antagonism on retinal vascular pathology. Circ Res. 2009;104:124–33.CrossRefPubMed

20.

Wilkinson-Berka JL, Agrotis A, Deliyanti D. The retinal renin-angiotensin system: role of angiotensin II and aldosterone. Peptides. 2012;36:142–50.CrossRefPubMed

21.

Nitta E, Hirooka K, Tenkumo K, Fujita T, Nishiyama A, Nakamura T, et al. Aldosterone: a mediator of retinal ganglion cell death and the potential role in the pathogenesis in normal-tension glaucoma. Cell Death Dis. 2013;4:e711.CrossRefPubMedPubMedCentral

22.

Rafiq K, Nakano D, Ihara G, Hitomo H, Fujisawa Y, Ohashi N, et al. Effects of mineralocorticoid receptor blockade on glucocorticoid-induced renal injury in adrenalectomized rats. J Hypertens. 2011;29:290–8.CrossRefPubMedPubMedCentral

23.

Rafiq K, Noma T, Fujisawa Y, Jshihara Y, Arai Y, Nabi AH, et al. Renal sympathetic denervation suppresses de novo podocyte injury and albuminuria in rats with aortic regurgitation. Circulation. 2012;125:1402–13.CrossRefPubMedPubMedCentral

24.

Woller G, Brandt E, Mittelstӓdt J, Rybakowski C, Petersen F. Platelet factor 4/CXCL4-stimulated human monocytes induce apoptosis in endothelial cells by the release of oxygen radicals. J Leukoc Biol. 2008;83:936–45.CrossRefPubMed

25.

Cohen RA, Vanhoutte PM. Endothelium-dependent hyperpolarization: beyond nitric oxide and cyclic GMP. Circulation. 1995;92:3337–49.CrossRefPubMed

26.

Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G. Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA. 1987;84:9265–9.CrossRefPubMedPubMedCentral

27.

Luksch A, Polak K, Beier C. Effects of systemic NO synthase inhibition on choroidal and optic nerve head blood flow in healthy subjects. Invest Ophthalmol Vis Sci. 2000;41:3080–4.PubMed

28.

Okuno T, Oku H, Suguyama T, Yang Y, Ikeda T. Evidence that nitric oxide is involved in autoregulation in optic nerve head of rabbits. Invest Ophthalmol Vis Sci. 2002;43:784–9.PubMed

29.

Yamazaki Y, Drance S. The relationship between progression of visual field defects and retrobulbar circulation in patients with glaucoma. Am J Ophthalmol. 1997;124:287–95.CrossRefPubMed

30.

Wang Y, Fawzi A, Varma R, Sadun AA, Zhang X, Tan O, et al. Pilot study of optical coherence tomography measurement of retinal blood flow in retinal and optic nerve diseases. Invest Ophthalmol Vis Sci. 2011;52:840–5.CrossRefPubMedPubMedCentral

31.

Lehmann K, Tschuor C, Rickenbacher A, Jang JH, Oberkofler CE, Tschopp O, et al. Liver failure after extended hepatectomy in mice is mediated by a p21-dependent barrier to liver regeneration. Gastroenterology. 2012;143:1609–19.CrossRefPubMed

32.

Willenbring H, Sharma AD, Vogel A, Lee AY, Rothfuss A, Wang Z, et al. Loss of p21 permits carcinogenesis from chronically damaged liver and kidney epithelial cells despite unchecked apoptosis. Cancer Cell. 2008;14:59–67.CrossRefPubMedPubMedCentral

33.

Wang DB, Kinoshita C, Kinoshita Y, Morrison RS. P53 and mitochondrial function in neurons. Biochim et Biophys Acta. 2014;1842:1186–97.CrossRef

34.

Shi H, Zhang A, He Y, Yang M, Gan W. Effect of p53 on aldosterone-induced mesangial cell apoptosis in vivo and in vitro. Mol Med Rep. 2016;13:5102–8.CrossRefPubMedPubMedCentral

35.

Murray-Zmijewski F, Lane DP, Bourdon JC. p53/p63/p73 isoforms: an orchestra of isoforms to harmonise cell differentiation and response to stress. Cell Death Differ. 2006;13:962–72.CrossRefPubMed

36.

Vousden KH, Prives C. Blinded by the light: the growing complexity of p53. Cell. 2009;137:413–31.CrossRefPubMed

37.

Mason RS, Reichrath J. Sunlight vitamin D and skin cancer. Anticancer Agents Med Chem. 2013;13:83–97.CrossRefPubMed

38.

Husain K, Ferder L, Mizobuchi M, Finch J, Slatopolsky E. Combination therapy with paricalcitol and enalapril ameliorates cardiac oxidative injury in uremic rats. Am J Nephrol. 2009;29:465–72.CrossRefPubMed

39.

Rehman S, Chandel N, Salhan D, Rai P, Sharma B, Singh T, et al. Ethanol and vitamin D receptor in T cell apoptosis. J Neuroimmune Pharmacol. 2013;8:251–61.CrossRefPubMed

40.

Zhao M, Valamanesh F, Celerier I, Savoldelli M, Jonet L, Jeanny JC, et al. The neuroretina is a novel mineralocorticoid target: aldosterone up-regulates ion and water channels in Müller glial cells. FASEB J. 2010;24:3405–15.CrossRefPubMed

Title: Gene expression changes in the retina after systemic administration of aldosterone
Authors: Aoi Ono
Kazuyuki Hirooka
Yuki Nakano
Eri Nitta
Akira Nishiyama
Akitaka Tsujikawa
Publication date: 01-07-2018
Publisher: Springer Japan
Published in: Japanese Journal of Ophthalmology / Issue 4/2018
Print ISSN: 0021-5155
Electronic ISSN: 1613-2246
DOI: https://doi.org/10.1007/s10384-018-0595-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Gene expression changes in the retina after systemic administration of aldosterone

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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