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Review
. 2016 Oct 20;29(1):7-16.
doi: 10.1016/j.joco.2016.09.009. eCollection 2017 Mar.

Therapeutic targets of renin-angiotensin system in ocular disorders

Rajesh Choudhary  1 , Mandeep Singh Kapoor  1 , Amrita Singh  1 , Surendra H Bodakhe  1
Affiliations
Review

Therapeutic targets of renin-angiotensin system in ocular disorders

Rajesh Choudhary et al. J Curr Ophthalmol. .

Abstract

Purpose: To review current literature on the renin-angiotensin system (RAS)-mediated pathogenic mechanisms and therapeutic targets in ocular diseases.

Methods: A comprehensive literature survey was performed on PubMed, Scopus, and Google Scholar databases published from 1977 to 2016. The search terms were a RAS, angiotensin, angiotensin receptor, prorenin, pro (renin) receptor, angiotensin converting enzyme inhibitor, angiotensin receptor blocker associated with ocular disorders like cataract, glaucoma, diabetic retinopathy (DR), macular degeneration, and uveitis. Articles were reviewed on the basis of the association between ocular disorders and RAS and relevant articles were discussed.

Results: The literature revealed that the individual RAS components including renin, angiotensins, angiotensin converting enzymes, and RAS receptors have been expressed in the specific ocular tissues like retina, choroid, and ciliary body. The activation of both circulatory and local RAS potentiate the various inflammatory and angiogenic signaling molecules, including vascular endothelial growth factor (VEGF), extracellular signal-regulated kinase, and advanced glycation end products (AGE) in the ocular tissues and leads to several blinding disorders like DR, glaucoma, and macular degeneration. The classical and newer RAS inhibitors have illustrated protective effects on blinding disorders, including DR, glaucoma, macular degeneration, uveitis, and cataract.

Conclusions: The RAS components are present in the extrarenal tissues including ocular tissue and have an imperative role in the ocular pathophysiology. The clinical studies are needed to show the role of therapeutic modalities targeting RAS in the treatment of different ocular disorders.

Keywords: (Pro) renin receptor; Angiotensin II; Angiotensin II type 1 receptor; Ocular disorders; Ocular renin-angiotensin system.

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Figures

Fig. 1
Fig. 1
Schematic representation of ocular renin-angiotensin system signaling cascades on the basis of literature., , , , , , , , , , , , , , , , , , , , , , , , , , , , , ACE: angiotensin-converting enzyme; ACE2: angiotensin-converting enzyme type 2; ACEIs: angiotensin-converting enzyme inhibitors; AGE: advanced glycation end products; Ang (1–7): angiotensin (1–7); Ang (1–9): angiotensin (1–9); Ang-I: angiotensin I; Ang-II: angiotensin II; AT1R: angiotensin II type 1 receptor; AT1RBs: angiotensin II type 1 receptor blockers; AT2R: angiotensin II type 2 receptor; cGMP/NO: cyclic guanosine mono phosphate/nitric oxide; DAG: diacyl glycerol; ERK1/2: extracellular signal regulated kinase 1/2; ICAM-1: Intercellular adhesion molecule-1; IP3: inositole-1,4,5-triphosphate; MAPK: mitogen-activated protein kinase; Mas R: Mas receptor; NFκB: nuclear factor kappa-light-chain-enhancer of activated B cells; PAI-1: plasminogen activator inhibitor-1; PK-C: protein kinase-C; PLA2: phospholipase-A2; PL-C: phospholipase-C; (P)RR: (pro)renin receptor; (P)RRBs: (pro)renin receptor blockers; TGF-β: transforming growth factor- β; VEGF: vascular endothelial growth factor.
See this image and copyright information in PMC

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