%0 Journal Article
%T Renin-Angiotensin System Hyperactivation Can Induce Inflammation and Retinal Neural Dysfunction
%A Toshihide Kurihara
%A Yoko Ozawa
%A Susumu Ishida
%A Hideyuki Okano
%A Kazuo Tsubota
%J International Journal of Inflammation
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/581695
%X The renin-angiotensin system (RAS) is a hormone system that has been classically known as a blood pressure regulator but is becoming well recognized as a proinflammatory mediator. In many diverse tissues, RAS pathway elements are also produced intrinsically, making it possible for tissues to respond more dynamically to systemic or local cues. While RAS is important for controlling normal inflammatory responses, hyperactivation of the pathway can cause neural dysfunction by inducing accelerated degradation of some neuronal proteins such as synaptophysin and by activating pathological glial responses. Chronic inflammation and oxidative stress are risk factors for high incidence vision-threatening diseases such as diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucoma. In fact, increasing evidence suggests that RAS inhibition may actually prevent progression of various ocular diseases including uveitis, DR, AMD, and glaucoma. Therefore, RAS inhibition may be a promising therapeutic approach to fine-tune inflammatory responses and to prevent or treat certain ocular and neurodegenerative diseases. 1. Introduction Most visual disorders occur in the retina, which is a part of the central nervous system (CNS) and consists of neurons, glia, pigment epithelium (RPE), and blood vessels. Currently, diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucoma are the top causes of blindness in the developed countries. These diseases can occur when local or systemic neuronal and vascular homeostasis mechanisms are dysregulated. The highest risk factor for many of these diseases is aging [1¨C3], and as is the case with other age-related diseases such as Alzheimer¡¯s disease, cardiovascular disease, cancer, arthritis, osteoporosis, and hypertension, accumulating evidence suggests that chronic inflammation and oxidative stress can accelerate or promote disease progression [4¨C6]. The renin-angiotensin system (RAS) is classically known as a systemic blood-pressure-regulating system. However, it is becoming widely recognized as an inflammation regulator as well. Independent of systemic RAS, tissue intrinsic RASs have been identified in various tissues (including the retina) and are important for maintaining local homeostasis. Elements of the RAS pathway are highly conserved in many species including invertebrates and humans demonstrating that its functions are evolutionarily conserved, although spatial expression patterns differ slightly between different species [7]. We have reported that angiotensin II type 1 receptor blocker
%U http://www.hindawi.com/journals/iji/2012/581695/