Reactive oxygen species, Nox and angiotensin II in angiogenesis: implications for retinopathy

Abstract

Pathological angiogenesis is a key feature of many diseases including retinopathies such as ROP (retinopathy of prematurity) and DR (diabetic retinopathy). There is considerable evidence that increased production of ROS (reactive oxygen species) in the retina participates in retinal angiogenesis, although the mechanisms by which this occurs are not fully understood. ROS is produced by a number of pathways, including the mitochondrial electron transport chain, cytochrome P450, xanthine oxidase and uncoupled nitric oxide synthase. The family of NADPH oxidase (Nox) enzymes are likely to be important given that their primary function is to produce ROS. Seven isoforms of Nox have been identified named Nox1-5, Duox (dual oxidase) 1 and Duox2. Nox1, Nox2 and Nox4 have been most extensively studied and are implicated in the development of conditions such as hypertension, cardiovascular disease and diabetic nephropathy. In recent years, evidence has accumulated to suggest that Nox1, Nox2 and Nox4 participate in pathological angiogenesis; however, there is no clear consensus about which Nox isoform is primarily responsible. In terms of retinopathy, there is growing evidence that Nox contribute to vascular injury. The RAAS (renin-angiotensin-aldosterone system), and particularly AngII (angiotensin II), is a key stimulator of Nox. It is known that a local RAAS exists in the retina and that blockade of AngII and aldosterone attenuate pathological angiogenesis in the retina. Whether the RAAS influences the production of ROS derived from Nox in retinopathy is yet to be fully determined. These topics will be reviewed with a particular emphasis on ROP and DR.

Pulmonary Surfactant Protein A Is Expressed in Mouse Retina by Muller Cells and Impacts Neovascularization in Oxygen-Induced Retinopathy

“…Inflammation in premature infants is a major cause of pulmonary and systemic disease. The developing retina is particularly vulnerable to excessive inflammation and reactive oxygen species 55 as multiple neuronal and vascular structures are not yet established at 23 weeks gestation in humans, 56 which is the current lowest gestational age at which infants are deemed viable. Thus, the entire vascular system of the retina may develop ex-utero in prematurely delivered infants and therefore must develop under highly stressed conditions.…”

Resveratrol ameliorates oxidative stress and inhibits aquaporin 4 expression following rat cerebral ischemia-reperfusion injury

“…The central event during cerebral ischemia is the generation of ROS, which results in damage to lipids, proteins and DNA, leading to neuronal death (3,4). In a variety of ROS-generating systems, inducible nitric oxide synthase (iNOS) serves a major role by promoting the production of activated oxygen under hypoxic conditions, then further disrupting the blood-brain barrier and leading to brain edema (5,6).…”

Calcium dobesilate for diabetic retinopathy: a systematic review and meta-analysis

“…Several oral medications, including aspirin [7], protein kinase C inhibitor [8], renin-angiotensin blockade [9] and candesartan [10], effectively inhibit early DR lesions. Calcium dobesilate (2,5-dihydroxybenzenesulfonate) was developed for DR and chronic venous insufficiency more than 40 years ago.…”