%0 Journal Article
%T Targeting Inflammation in Emerging Therapies for Genetic Retinal Disease
%A Ishaq A. Viringipurampeer
%A Abu E. Bashar
%A Cheryl Y. Gregory-Evans
%A Orson L. Moritz
%A Kevin Gregory-Evans
%J International Journal of Inflammation
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/581751
%X Genetic retinal diseases such as age-related macular degeneration and monogenic diseases such as retinitis pigmentosa account for some of the commonest causes of blindness in the developed world. Diverse genetic abnormalities and environmental causes have been implicated in triggering multiple pathological mechanisms such as oxidative stress, lipofuscin deposits, neovascularisation, and programmed cell death. In recent years, inflammation has also been highlighted although whether inflammatory mediators play a central role in pathogenesis or a more minor secondary role has yet to be established. Despite this, numerous interventional studies, particularly targeting the complement system, are underway with the promise of novel therapeutic strategies for these important blinding conditions. 1. Introduction Inherited retinal diseases include some of the commonest causes of blindness in the developed world [1, 2]. Prominent examples included age-related macular degeneration (AMD), diabetic retinopathy, and the numerous monogenic conditions such as retinitis pigmentosa (RP), Stargardt¡¯s disease, and X-linked retinoschisis. As well as causative/predisposing genetic abnormalities [3], in some cases (such as AMD), environmental factors such as smoking and diet have been highlighted [4, 5]. These aetiological factors have been associated with diverse abnormal biochemical pathways in the degenerating retina, for instance, oxidative stress [6]; lipofuscin accumulation in the retinal pigment epithelium [7]; abnormalities of the extracellular matrix [8]; mitochondrial abnormalities [9]; ischaemia with neovascularisation [10]; programmed cell death [11]. In particular in AMD and RP, inflammation has recently become a prominent member of this list of abnormal pathological pathways triggered by genetic retinal disease [12, 13]. 2. Established Links between Inflammation and Genetic Retinal Disease Early studies showed that autoantibodies can be detected in blood of AMD patients [14, 15] and that macrophages also accumulate in the choroid [16] which suggested that immune-mediated processes were involved in the pathogenesis of AMD. Renewed interest in inflammation in genetic retinal disease was, however, more recently triggered by the discovery of elements of the immune system and multiple proteins of the complement pathway within the drusen seen in AMD [17]. Although the exact pathophysiology of AMD remains largely unknown, accumulation of drusen is acknowledged as an early and major pathological hallmark of the disease, preempting damage in the retinal pigment
%U http://www.hindawi.com/journals/iji/2013/581751/