Mineralocorticoid receptor in ocular fundus diseases_Chinese Journal of Ocular Fundus Diseases

Authors：

Li Xinxin ,  Xu Xun

Department of Ophthalmology, Shanghai General Hospital affiliated to Shanghai Jiao Tong University, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai 200080, China;

Corresponding author：

Xu Xun, Email: drxuxun@sjtu.edu.cn

Keywords：

Receptors, mineralocorticoid; Central serous chorioretinopathy/therapy; Ocular fundus diseases

DOI：

10.3760/cma.j.issn.1005-1015.2018.01.029

Video：

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Abstract Full text Figures/Tables Video References Cited by

The mineralocorticoid receptor (MR) belongs to the nuclear receptor superfamily and is expressed in the retina and choroid. MR antagonist (MRA) has a long history of application in non-ophthalmic clinical practice. Various cellular and animal models indicated that inappropriate activation of MR participated in pathological angiogenesis, oxidative stress, inflammation, disturbance of ion/water homeostasis and neurodegenerative changes, while the application of MRA can reduce or reverse these pathological processes. After using MRA in central serous chorioretinopathy (CSC) patients, improved visual function, less subretinal fluid and reduced sub-foveal choroidal thickness were observed. Single nucleotide polymorphisms in MR and plasma aldosterone levels were significantly different between chronic CSC patients and CSC patients with spontaneous remission. Novel formulation for sustained-release MRA and the mechanisms involving inflammation may become the new focus of MR study. This review summarizes the research status of MR and MRA in order to provide a reference for future basic research and clinical treatment.

Citation： Li Xinxin, Xu Xun. Mineralocorticoid receptor in ocular fundus diseases. Chinese Journal of Ocular Fundus Diseases, 2018, 34(1): 96-99. doi: 10.3760/cma.j.issn.1005-1015.2018.01.029 Copy

1.	Lad EM, Hammill BG, Qualls LG, et al. Anti-VEGF treatment patterns for neovascular age-related macular degeneration among medicare beneficiaries[J]. Am J Ophthalmol, 2014, 158(3): 537-543. DOI: 10.1016/j.ajo.2014.05.014.
2.	Wong RL, Lai TY. Polypoidal choroidal vasculopathy: an update on therapeutic approaches [J]. J Ophthalmic Vis Res, 2013, 8(4): 359-371.
3.	Daruich A, Matet A, Dirani A, et al. Central serous chorioretinopathy: recent findings and new physiopathology hypothesis [J]. Prog Retin Eye Res, 2015, 48: 82-118. DOI: 10.1016/j.preteyeres.2015.05.003.
4.	MacDonald D.The ABCs of RVO: a review of retinal venous occlusion [J]. Clin Exp Optom, 2014. 97(4): 311-323. DOI: 10.1111/cxo.12120.
5.	Behar-Cohen F, Zhao M. Corticosteroids and the retina: a role for the mineralocorticoid receptor [J]. Curr Opin Neurol, 2016, 29(1): 49-54. DOI: 10.1097/WCO.0000000000000284.
6.	Collingwood TN, Urnov FD, Wolffe AP. Nuclear receptors: coactivators, corepressors and chromatin remodeling in the control of transcription[J]. J Mol Endocrinol, 1999, 23(3): 255-275.
7.	Evans RM. The steroid and thyroid hormone receptor superfamily[J]. Science, 1988, 240(4854): 889-895.
8.	Ribeiro RC, Kushner PJ, Baxter JD. The nuclear hormone receptor gene superfamily [J]. Annu Rev Med, 1995, 46: 443-453. DOI: 10.1146/annurev.med.46.1.443.
9.	Pippal JB, Fuller PJ. Structure-function relationships in the mineralocorticoid receptor[J]. J Mol Endocrinol, 2008, 41(6): 405-413. DOI: 10.1677/JME-08-0093.
10.	Viengchareun S, Le Menuet D, Martinerie L, et al.The mineralocorticoid receptor: insights into its molecular and (patho)physiological biology[J]. Nucl Recept Signal, 2007, 5: 12. DOI: 10.1621/nrs.05012.
11.	Farman N, Rafestin-Oblin ME. Multiple aspects of mineralocorticoid selectivity[J]. Am J Physiol Renal Physiol, 2001, 280(2): 181-192.
12.	Ueda K, Nagase M.Mineralocorticoid receptor activation as an etiological factor in kidney diseases[J]. Clin Exp Nephrol, 2014, 18(1): 16-23.DOI: 10.1007/s10157-013-0827-3.
13.	Huang LL, Nikolic-Paterson DJ, Han Y, et al.Myeloid mineralocorticoid receptor activation contributes to progressive kidney disease[J]. J Am Soc Nephrol, 2014, 25(10): 2231-2240. DOI: 10.1681/ASN.2012111094.
14.	Bauersachs J, Jaisser F, Toto R.Mineralocorticoid receptor activation and mineralocorticoid receptor antagonist treatment in cardiac and renal diseases[J]. Hypertension, 2015, 65(2): 257-263. DOI: 10.1161/HYPERTENSIONAHA.114.04488.
15.	Jaisser F, Farman N.Emerging roles of the mineralocorticoid receptor in pathology: toward new paradigms in clinical pharmacology[J]. Pharmacol Rev, 2016, 68(1): 49-75. DOI: 10.1124/pr.115.011106.
16.	Mirshahi M, Nicolas C, Mirshahi A, et al.The mineralocorticoid hormone receptor and action in the eye [J]. Biochem Biophys Res Commun, 1996, 219(1): 150-156. DOI: 10.1006/bbrc.1996.0197.
17.	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(1): 124-133. DOI: 10.1161/CIRCRESAHA.108.176008.
18.	Bousquet E, Zhao M, Ly A, et al.The aldosterone-mineralocorticoid receptor pathway exerts anti-inflammatory effects in endotoxin-induced uveitis [J/OL]. PLoS One, 2012, 7(11): 49036 [2012-11-09]. https://doi.org/10.1371/journal.pone.0049036.DOI:10.1371/journal.pone.0049036.
19.	Arriza JL, Weinberger C, Cerelli G, et al. Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor [J]. Science, 1987, 237(4812): 268-275.
20.	Kolkhof P, Borden SA. Molecular pharmacology of the mineralocorticoid receptor: prospects for novel therapeutics [J]. Mol Cell Endocrinol, 2012, 350(2): 310-317. DOI: 10.1016/j.mce.2011.06.025.
21.	Menard J. The 45-year story of the development of an anti-aldosterone more specific than spironolactone[J]. Mol Cell Endocrinol, 2004, 217(1-2): 45-52. DOI: 10.1016/j.mce.2003.10.008.
22.	Colussi G, Catena C, Sechi LA. Spironolactone, eplerenone and the new aldosterone blockers in endocrine and primary hypertension[J]. J Hypertens, 2013, 31(1): 3-15. DOI: 10.1097/HJH.0b013e3283599b6a.
23.	Capuano A, Scavone C, Vitale C, et al.Mineralocorticoid receptor antagonists in heart failure with preserved ejection fraction (HFpEF) [J]. Int J Cardiol, 2015, 200: 15-19. DOI: 10.1016/j.ijcard.2015.07.038.
24.	Parthasarathy HK, Menard J, White WB, et al.A double-blind, randomized study comparing the antihypertensive effect of eplerenone and spironolactone in patients with hypertension and evidence of primary aldosteronism [J]. J Hypertens, 2011, 29(5): 980-890. DOI: 10.1097/HJH.0b013e3283455ca5.
25.	Armanini D, Sabbadin C, Dona G, et al.Aldosterone receptor blockers spironolactone and canrenone: two multivalent drugs [J]. Expert Opin Pharmacother, 2014, 15(7): 909-912. DOI: 10.1517/14656566.2014.896901.
26.	Pitt B, Kober L, Ponikowski P, et al.Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial [J]. Eur Heart J, 2013, 34(31): 2453-2463. DOI: 10.1093/eurheartj/eht187.
27.	Pitt B, Anker SD, Bohm M, et al. Rationale and design of MinerAlocorticoid Receptor antagonist Tolerability Study-Heart Failure (ARTS-HF): a randomized study of finerenone vs. eplerenone in patients who have worsening chronic heart failure with diabetes and/or chronic kidney disease[J]. Eur J Heart Fail, 2015, 17(2): 224-232. DOI: 10.1002/ejhf.218.
28.	Bakris GL, Agarwal R, Chan JC, et al. Effect of finerenone on albuminuria in patients with diabetic nephropathy: a randomized clinical trial[J]. JAMA, 2015, 314(9): 884-894. DOI: 10.1001/jama.2015.10081.
29.	Collin M, Niemann F, Jaisser F.Mineralocorticoid receptor modulators: a patent review (2007-2012)[J]. Expert Opin Ther Pat, 2014, 24(2): 177-183. DOI: 10.1517/13543776.2014.854772.
30.	Zhao M, Valamanesh F, Celerier I, et al.The neuroretina is a novel mineralocorticoid target: aldosterone up-regulates ion and water channels in Müller glial cells[J]. FASEB J, 2010, 24(9): 3405-3415. DOI: 10.1096/fj.09-154344.
31.	Zhao M, Celerier I, Bousquet E, et al.Mineralocorticoid receptor is involved in rat and human ocular chorioretinopathy[J]. J Clin Invest, 2012, 122(7): 2672-2679. DOI: 10.1172/JCI61427.
32.	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(1): 116-123. DOI: 10.1016/j.exer.2011.12.012.
33.	Nitta E, Hirooka K, Tenkumo K, et al.Aldosterone: a mediator of retinal ganglion cell death and the potential role in the pathogenesis in normal-tension glaucoma[J]. Cell Death Dis, 2013, 4: 711. DOI: 10.1038/cddis.2013.240.
34.	Bousquet E, Beydoun T, Rothschild PR, et al.Spironolactone for nonresolving central serous chorioretinopathy: a randomized controlled crossover study[J]. Retina, 2015, 35(12): 2505-2515. DOI: 10.1097/IAE.0000000000000614.
35.	Ghadiali Q, Jung JJ, Yu S, et al. Central serous chorioretinopathy treated with mineralocorticoid antagonists: a one-year pilot study[J]. Retina, 2016, 36(3): 611-618. DOI: 10.1097/IAE.0000000000000748.
36.	Bousquet E, Beydoun T, Zhao M, et al.Mineralocorticoid receptor antagonism in the treatment of chronic central serous chorioretinopathy: a pilot study[J]. Retina, 2013, 33(10): 2096-2102. DOI: 10.1097/IAE.0b013e318297a07a.
37.	Breukink MB, den Hollander AI, Keunen JE, et al.The use of eplerenone in therapy-resistant chronic central serous chorioretinopathy[J]. Acta Ophthalmol, 2014, 92(6): 488-490. DOI: 10.1111/aos.12392.
38.	Chin EK, Almeida DR, Roybal CN, et al.Oral mineralocorticoid antagonists for recalcitrant central serous chorioretinopathy[J]. Clin Ophthalmol, 2015, 9: 1449-1456. DOI: 10.2147/OPTH.S86778.
39.	Herold TR, Prause K, Wolf A, et al. Spironolactone in the treatment of central serous chorioretinopathy-a case series[J].Graefe's Arch Clin Exp Ophthalmol, 2014, 252(12): 1985-1991. DOI: 10.1007/s00417-014-2780-6.
40.	Maier M, Stumpfe S, Feucht N, et al.Mineralocorticoid receptor antagonists as treatment option for acute and chronic central serous chorioretinopathy[J].Ophthalmologe, 2014, 111(2): 173-180. DOI: 10.1007/s00347-013-3001-0.
41.	Singh RP, Sears JE, Bedi R, et al. Oral eplerenone for the management of chronic central serous chorioretinopathy[J]. Int J Ophthalmol, 2015, 8(2): 310-314. DOI: 10.3980/j.issn.2222-3959.2015.02.17.
42.	Gong Q, Sun XH, Yuan ST, et al.The relation of the serum aldosterone level and central serous chorioretinopathy-a pilot study[J]. Eur Rev Med Pharmacol Sci, 2017, 21(3): 446-453.
43.	van Dijk EHC, Schellevis RL, van Bergen M, et al. Association of a haplotype in the NR3C2 gene, encoding the mineralocorticoid receptor, with chronic central serous chorioretinopathy[J]. JAMA Ophthalmol, 2017, 135(5): 446-451. DOI: 10.1001/jamaophthalmol.2017.0245.
44.	Kapoor KG, Sim J.Spironolactone as an adjunctive treatment in neovascular age-related macular degeneration[J]. Case Rep Ophthalmol, 2017, 8(2): 314-320. DOI: 10.1159/000475880.
45.	Zhao M, Rodriguez-Villagra E, Kowalczuk L, et al.Tolerance of high and low amounts of PLGA microspheres loaded with mineralocorticoid receptor antagonist in retinal target site[J]. J Control Release, 2017, 266: 187-197. DOI:10.1016/j.jconrel.2017.09.029.
46.	Liegl R, Ulbig MW.Central serous chorioretinopathy[J]. Ophthalmologica, 2014, 232(2): 65-76. DOI:10.1159/000360014.
47.	Kapoor KG, Wagner AL.mineralocorticoid antagonists in the treatment of central serous chorioretinopathy: a comparative analysis[J]. Ophthalmic Res, 2016, 56(1): 17-22. DOI: 10.1159/000444058.
48.	Pichi F, Carrai P, Ciardella A, et al.Comparison of two mineralcorticosteroids receptor antagonists for the treatment of central serous chorioretinopathy[J/OL]. Int Ophthalmol, 2016, 2016: E1[2016-10-18]. https://link.springer.com/article/10.1007%2Fs10792-016-0377-2.DOI: 10.1007/s10792-016-0377-2.[published online ahead of print].

1. Lad EM, Hammill BG, Qualls LG, et al. Anti-VEGF treatment patterns for neovascular age-related macular degeneration among medicare beneficiaries[J]. Am J Ophthalmol, 2014, 158(3): 537-543. DOI: 10.1016/j.ajo.2014.05.014.
2. Wong RL, Lai TY. Polypoidal choroidal vasculopathy: an update on therapeutic approaches [J]. J Ophthalmic Vis Res, 2013, 8(4): 359-371.
3. Daruich A, Matet A, Dirani A, et al. Central serous chorioretinopathy: recent findings and new physiopathology hypothesis [J]. Prog Retin Eye Res, 2015, 48: 82-118. DOI: 10.1016/j.preteyeres.2015.05.003.
4. MacDonald D.The ABCs of RVO: a review of retinal venous occlusion [J]. Clin Exp Optom, 2014. 97(4): 311-323. DOI: 10.1111/cxo.12120.
5. Behar-Cohen F, Zhao M. Corticosteroids and the retina: a role for the mineralocorticoid receptor [J]. Curr Opin Neurol, 2016, 29(1): 49-54. DOI: 10.1097/WCO.0000000000000284.
6. Collingwood TN, Urnov FD, Wolffe AP. Nuclear receptors: coactivators, corepressors and chromatin remodeling in the control of transcription[J]. J Mol Endocrinol, 1999, 23(3): 255-275.
7. Evans RM. The steroid and thyroid hormone receptor superfamily[J]. Science, 1988, 240(4854): 889-895.
8. Ribeiro RC, Kushner PJ, Baxter JD. The nuclear hormone receptor gene superfamily [J]. Annu Rev Med, 1995, 46: 443-453. DOI: 10.1146/annurev.med.46.1.443.
9. Pippal JB, Fuller PJ. Structure-function relationships in the mineralocorticoid receptor[J]. J Mol Endocrinol, 2008, 41(6): 405-413. DOI: 10.1677/JME-08-0093.
10. Viengchareun S, Le Menuet D, Martinerie L, et al.The mineralocorticoid receptor: insights into its molecular and (patho)physiological biology[J]. Nucl Recept Signal, 2007, 5: 12. DOI: 10.1621/nrs.05012.
11. Farman N, Rafestin-Oblin ME. Multiple aspects of mineralocorticoid selectivity[J]. Am J Physiol Renal Physiol, 2001, 280(2): 181-192.
12. Ueda K, Nagase M.Mineralocorticoid receptor activation as an etiological factor in kidney diseases[J]. Clin Exp Nephrol, 2014, 18(1): 16-23.DOI: 10.1007/s10157-013-0827-3.
13. Huang LL, Nikolic-Paterson DJ, Han Y, et al.Myeloid mineralocorticoid receptor activation contributes to progressive kidney disease[J]. J Am Soc Nephrol, 2014, 25(10): 2231-2240. DOI: 10.1681/ASN.2012111094.
14. Bauersachs J, Jaisser F, Toto R.Mineralocorticoid receptor activation and mineralocorticoid receptor antagonist treatment in cardiac and renal diseases[J]. Hypertension, 2015, 65(2): 257-263. DOI: 10.1161/HYPERTENSIONAHA.114.04488.
15. Jaisser F, Farman N.Emerging roles of the mineralocorticoid receptor in pathology: toward new paradigms in clinical pharmacology[J]. Pharmacol Rev, 2016, 68(1): 49-75. DOI: 10.1124/pr.115.011106.
16. Mirshahi M, Nicolas C, Mirshahi A, et al.The mineralocorticoid hormone receptor and action in the eye [J]. Biochem Biophys Res Commun, 1996, 219(1): 150-156. DOI: 10.1006/bbrc.1996.0197.
17. 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(1): 124-133. DOI: 10.1161/CIRCRESAHA.108.176008.
18. Bousquet E, Zhao M, Ly A, et al.The aldosterone-mineralocorticoid receptor pathway exerts anti-inflammatory effects in endotoxin-induced uveitis [J/OL]. PLoS One, 2012, 7(11): 49036 [2012-11-09]. https://doi.org/10.1371/journal.pone.0049036.DOI:10.1371/journal.pone.0049036.
19. Arriza JL, Weinberger C, Cerelli G, et al. Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor [J]. Science, 1987, 237(4812): 268-275.
20. Kolkhof P, Borden SA. Molecular pharmacology of the mineralocorticoid receptor: prospects for novel therapeutics [J]. Mol Cell Endocrinol, 2012, 350(2): 310-317. DOI: 10.1016/j.mce.2011.06.025.
21. Menard J. The 45-year story of the development of an anti-aldosterone more specific than spironolactone[J]. Mol Cell Endocrinol, 2004, 217(1-2): 45-52. DOI: 10.1016/j.mce.2003.10.008.
22. Colussi G, Catena C, Sechi LA. Spironolactone, eplerenone and the new aldosterone blockers in endocrine and primary hypertension[J]. J Hypertens, 2013, 31(1): 3-15. DOI: 10.1097/HJH.0b013e3283599b6a.
23. Capuano A, Scavone C, Vitale C, et al.Mineralocorticoid receptor antagonists in heart failure with preserved ejection fraction (HFpEF) [J]. Int J Cardiol, 2015, 200: 15-19. DOI: 10.1016/j.ijcard.2015.07.038.
24. Parthasarathy HK, Menard J, White WB, et al.A double-blind, randomized study comparing the antihypertensive effect of eplerenone and spironolactone in patients with hypertension and evidence of primary aldosteronism [J]. J Hypertens, 2011, 29(5): 980-890. DOI: 10.1097/HJH.0b013e3283455ca5.
25. Armanini D, Sabbadin C, Dona G, et al.Aldosterone receptor blockers spironolactone and canrenone: two multivalent drugs [J]. Expert Opin Pharmacother, 2014, 15(7): 909-912. DOI: 10.1517/14656566.2014.896901.
26. Pitt B, Kober L, Ponikowski P, et al.Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial [J]. Eur Heart J, 2013, 34(31): 2453-2463. DOI: 10.1093/eurheartj/eht187.
27. Pitt B, Anker SD, Bohm M, et al. Rationale and design of MinerAlocorticoid Receptor antagonist Tolerability Study-Heart Failure (ARTS-HF): a randomized study of finerenone vs. eplerenone in patients who have worsening chronic heart failure with diabetes and/or chronic kidney disease[J]. Eur J Heart Fail, 2015, 17(2): 224-232. DOI: 10.1002/ejhf.218.
28. Bakris GL, Agarwal R, Chan JC, et al. Effect of finerenone on albuminuria in patients with diabetic nephropathy: a randomized clinical trial[J]. JAMA, 2015, 314(9): 884-894. DOI: 10.1001/jama.2015.10081.
29. Collin M, Niemann F, Jaisser F.Mineralocorticoid receptor modulators: a patent review (2007-2012)[J]. Expert Opin Ther Pat, 2014, 24(2): 177-183. DOI: 10.1517/13543776.2014.854772.
30. Zhao M, Valamanesh F, Celerier I, et al.The neuroretina is a novel mineralocorticoid target: aldosterone up-regulates ion and water channels in Müller glial cells[J]. FASEB J, 2010, 24(9): 3405-3415. DOI: 10.1096/fj.09-154344.
31. Zhao M, Celerier I, Bousquet E, et al.Mineralocorticoid receptor is involved in rat and human ocular chorioretinopathy[J]. J Clin Invest, 2012, 122(7): 2672-2679. DOI: 10.1172/JCI61427.
32. 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(1): 116-123. DOI: 10.1016/j.exer.2011.12.012.
33. Nitta E, Hirooka K, Tenkumo K, et al.Aldosterone: a mediator of retinal ganglion cell death and the potential role in the pathogenesis in normal-tension glaucoma[J]. Cell Death Dis, 2013, 4: 711. DOI: 10.1038/cddis.2013.240.
34. Bousquet E, Beydoun T, Rothschild PR, et al.Spironolactone for nonresolving central serous chorioretinopathy: a randomized controlled crossover study[J]. Retina, 2015, 35(12): 2505-2515. DOI: 10.1097/IAE.0000000000000614.
35. Ghadiali Q, Jung JJ, Yu S, et al. Central serous chorioretinopathy treated with mineralocorticoid antagonists: a one-year pilot study[J]. Retina, 2016, 36(3): 611-618. DOI: 10.1097/IAE.0000000000000748.
36. Bousquet E, Beydoun T, Zhao M, et al.Mineralocorticoid receptor antagonism in the treatment of chronic central serous chorioretinopathy: a pilot study[J]. Retina, 2013, 33(10): 2096-2102. DOI: 10.1097/IAE.0b013e318297a07a.
37. Breukink MB, den Hollander AI, Keunen JE, et al.The use of eplerenone in therapy-resistant chronic central serous chorioretinopathy[J]. Acta Ophthalmol, 2014, 92(6): 488-490. DOI: 10.1111/aos.12392.
38. Chin EK, Almeida DR, Roybal CN, et al.Oral mineralocorticoid antagonists for recalcitrant central serous chorioretinopathy[J]. Clin Ophthalmol, 2015, 9: 1449-1456. DOI: 10.2147/OPTH.S86778.
39. Herold TR, Prause K, Wolf A, et al. Spironolactone in the treatment of central serous chorioretinopathy-a case series[J].Graefe's Arch Clin Exp Ophthalmol, 2014, 252(12): 1985-1991. DOI: 10.1007/s00417-014-2780-6.
40. Maier M, Stumpfe S, Feucht N, et al.Mineralocorticoid receptor antagonists as treatment option for acute and chronic central serous chorioretinopathy[J].Ophthalmologe, 2014, 111(2): 173-180. DOI: 10.1007/s00347-013-3001-0.
41. Singh RP, Sears JE, Bedi R, et al. Oral eplerenone for the management of chronic central serous chorioretinopathy[J]. Int J Ophthalmol, 2015, 8(2): 310-314. DOI: 10.3980/j.issn.2222-3959.2015.02.17.
42. Gong Q, Sun XH, Yuan ST, et al.The relation of the serum aldosterone level and central serous chorioretinopathy-a pilot study[J]. Eur Rev Med Pharmacol Sci, 2017, 21(3): 446-453.
43. van Dijk EHC, Schellevis RL, van Bergen M, et al. Association of a haplotype in the NR3C2 gene, encoding the mineralocorticoid receptor, with chronic central serous chorioretinopathy[J]. JAMA Ophthalmol, 2017, 135(5): 446-451. DOI: 10.1001/jamaophthalmol.2017.0245.
44. Kapoor KG, Sim J.Spironolactone as an adjunctive treatment in neovascular age-related macular degeneration[J]. Case Rep Ophthalmol, 2017, 8(2): 314-320. DOI: 10.1159/000475880.
45. Zhao M, Rodriguez-Villagra E, Kowalczuk L, et al.Tolerance of high and low amounts of PLGA microspheres loaded with mineralocorticoid receptor antagonist in retinal target site[J]. J Control Release, 2017, 266: 187-197. DOI:10.1016/j.jconrel.2017.09.029.
46. Liegl R, Ulbig MW.Central serous chorioretinopathy[J]. Ophthalmologica, 2014, 232(2): 65-76. DOI:10.1159/000360014.
47. Kapoor KG, Wagner AL.mineralocorticoid antagonists in the treatment of central serous chorioretinopathy: a comparative analysis[J]. Ophthalmic Res, 2016, 56(1): 17-22. DOI: 10.1159/000444058.
48. Pichi F, Carrai P, Ciardella A, et al.Comparison of two mineralcorticosteroids receptor antagonists for the treatment of central serous chorioretinopathy[J/OL]. Int Ophthalmol, 2016, 2016: E1[2016-10-18]. https://link.springer.com/article/10.1007%2Fs10792-016-0377-2.DOI: 10.1007/s10792-016-0377-2.[published online ahead of print].

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