The renin-angiontensin system and the development of new antiglaucoma medications
Aline Ruilowa de Pinho Coelho, Rodrigo da Silva Santos, Angela Adamski da Silva Reis, Valeria Batista Boreck Seki, Jayter Silva Paula

Abstract
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TopicsCancer Mechanisms and Therapy · 14-3-3 protein interactions · Renin-Angiotensin System Studies
Dear editor;
We have read the article entitled “Aqueous humor renin, angiotensin I, and angiotensin II activity in primary open-angle glaucoma”^(1)^ published in this esteemed journal. We would like to commend the authors because this is a well-written article with an extremely relevant theme. Additionally, we would like to raise few points regarding this study.
The selection of study participants could have followed specific exclusion criteria. The use of oral beta-blockers is known to weaken the response of intraocular pressure reduction when used concomitantly with beta-blocker eye drops for the treatment of glaucoma^(2)^. In addition, the use of beta-blocker eye drops in most participants with primary open-angle glaucoma may have influenced the final result of the concentration of renin being lower in the aqueous humor of participants with cataract and glaucoma than in the control group (i.e., patients with cataract only). The results presented by the authors contradict the current literature. Thus, for the intervention, it is best to withdraw treatment with beta-blocker eye drops for 15 days before collecting the aqueous humor. In cases where it is not possible to completely withdraw the medication, the beta-blocker eye drops can be substituted for another class of antiglaucomatous eye drops which does not directly interfere with renin activity.
Other important aspects that were not considered in the article are the participants’ stage of glaucoma and the number of topical medications for glaucoma that each participant was using at the time of the research. The ethnicities of the study participants were also not taken into account. This is important because black patients, for example, respond less to angiotensin-converting enzyme (ACE) inhibitors than white hypertensive patients. Furthermore, antihypertensive medications have similar dose-related effects among both black and white patients, but these are achieved at higher doses in the former^(3)^. Therefore, the doses of antihypertensive medications should also have been considered.
Angiotensin II has been implicated in retinal vascular diseases, such as retinopathy of prematurity and diabetic retinopathy, and recent studies on its relationship with neovascularization and glaucoma have emerged^(4)^. The reduction in angiotensin II production promoted by ACE inhibitors achieves a similar effect to beta-blockers, which reduce the activity of plasma renin^(5)^. It is up to us researchers to determine if the renin-angiotensin system is indeed involved in the pathogenesis of glaucoma, and, if possible, eventually develop new antiglaucoma medications with ACE inhibitors.
The reference list from the paper itself. Each links out to its DOI / PubMed record.
- 1Seki VBB de Souza GR Messias A Casarini DE de Paula JS. Aqueous humor renin, angiotensin I, and angiotensin II activity in primary open-angle glaucoma Arq Bras Oftalmol 20208343183223275678310.5935/0004-2749.20200052 PMC 11826583 · doi ↗ · pubmed ↗
- 2Schuman JS. Effects of systemic b-blocker therapy on the efficacy and safety of topical brimonidine and timolol Ophthalmology 20001076117111771085783910.1016/s 0161-6420(00)00081-6 · doi ↗ · pubmed ↗
- 3Weir MR Gray JM Paster R Saunders E. Differing mechanisms of action of angiotensin-converting inhibition in black and white hypertensive patients. The Trandolapril Multicenter Study Group Hypertension 1995261124130760771510.1161/01.hyp.26.1.124 · doi ↗ · pubmed ↗
- 4Fletcher EL Phipps JA Ward MM Vessey KA Wilkinson-Berka JL. The renin-angiotensin system in retinal health and disease: Its influence on neurons, glia, and the vasculature Prog Retin Eye Res 2010294284311.5Ribeiro JM, Florêncio LP. Pharmacological blockade of the renin-angiotensin-aldosterone system: Conversion enzyme inhibition and AT 1 receptor antagonism. Rev Bras Hipertens. 2000;7(3):29-302.2038089010.1016/j.preteyeres.2010.03.003 · doi ↗ · pubmed ↗
- 5Coelho ARPC Santos RS Reis AAS The renin-angiontensin system and the development of new antiglaucoma medications Arq Bras Oftalmol.2021 Nov.10.5935/0004-2749.20220095 PMC 1182656835416904 · doi ↗ · pubmed ↗
- 6Seki VBB Souza GR Messias A Casarini DE Paula JS Aqueous humor renin, angiotensin I, and angiotensin II activity in primary open-angle glaucoma Arq Bras Oftalmol.2020 Aug 83(4)3183223275678310.5935/0004-2749.20200052 PMC 11826583 · doi ↗ · pubmed ↗
- 7Wang RF Podos SM Serle JB Baltatu OC Effect of SPP 635, a renin inhibitor, on intraocular pressure in glaucomatous monkey eyes Exp Eye Res.201294(1)14692217320610.1016/j.exer.2011.11.019 · doi ↗ · pubmed ↗
- 8Holappa M Vapaatalo H Vaajanen A Many Faces of Renin-angiotensin System - Focus on Eye Open Ophthalmol J.2017 Jun 19111221422876156610.2174/1874364101711010122 PMC 5510558 · doi ↗ · pubmed ↗
