Many Faces of Renin-angiotensin System - Focus on Eye

Abstract

The renin-angiotensin system (RAS), that is known for its role in the regulation of blood pressure as well as in fluid and electrolyte homeostasis, comprises dozens of angiotensin peptides and peptidases and at least six receptors. Six central components constitute the two main axes of the RAS cascade. Angiotensin (1-7), an angiotensin converting enzyme 2 and Mas receptor axis (ACE2-Ang(1-7)-MasR) counterbalances the harmful effects of the angiotensin II, angiotensin converting enzyme 1 and angiotensin II type 1 receptor axis (ACE1-AngII-AT1R) Whereas systemic RAS is an important factor in blood pressure regulation, tissue-specific regulatory system, responsible for long term regional changes, that has been found in various organs. In other words, RAS is not only endocrine but also complicated autocrine system. The human eye has its own intraocular RAS that is present e.g. in the structures involved in aqueous humor dynamics. Local RAS may thus be a target in the development of new anti-glaucomatous drugs. In this review, we first describe the systemic RAS cascade and then the local ocular RAS especially in the anterior part of the eye.

Keywords: ACE1; ACE2; Angiotensin (1-7); Angiotensin II; Eye; Glaucoma; Intraocular pressure; Mas receptor; Renin-angiotensin system.

Fig. (1)

The renin-angiotensin system. The two main axes of RAS are highlighted with colors. ACE2-Ang(1-7)-MasR axis (red lines) counterbalances the harmful effects of the ACE1-Ang II-AT1R axis (blue lines). ACE1: Angiotensin-converting enzyme 1; ACE2: Angiotensin-converting enzyme related carboxypeptidase; Ang I, II, III, IV: Angiotensin I, II, III, IV; Ang A: Angiotensin A; AT1R, -2R, -4R: Angiotensin II type 1, -2, -4 receptor; AP: Aminopeptidase (-A, -N, -M, -B); B1/B2: Bradykinin receptors; CAGE: Chymostatin-sensitive Ang II generating enzyme; CP: Carboxypeptidase; EP: Endopeptidase; Mas receptor: Ang(1-7) receptor type; NEP: Neprilysin; PEP: Prolyl-endopeptidase; PCP: Prolyl-carboxypeptidase; tPA: Tissue-type plasminogen activator. In angiotensin peptides the numbers in parenthesis refers to the numbers of amino acid residues. The figure is updated from Vaajanen et al. [41].