Mechanism of inflammation in age-related macular degeneration

Abstract

Age-related macular degeneration (AMD) is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease.

Figure 1

Normal human macula. (a) Schematic cross-sectional illustration of the macular outer segment and, in particular, the cells of the retinal pigment epithelium ((1) nucleus, (2) mitochondria, (3) ribosomes, (4) lysosomes, (5) Golgi apparatus, (6) melanosomes, (7) lipofuscin granules, (8) zonula occludens, (9) photoreceptor (cone), (10) outer segment of cones, (11) phagocytosis of photoreceptorial discs, (12) phagosome, (13) Bruch's membrane, and (14) choriocapillaris). (b) Fluorescein angiography of the macula with its foveal avascular zone (extracted and modified from [4]).

Figure 2

Early age-related macular degeneration. (a) Schematic cross-sectional illustration of the macula with an early stage of the disease ((1) drusen). (b) Fluorescein angiography of the macula affected by an early form of the disease (nonconfluent hard drusen); in this eye, the best best-correct visual acuity was 20/20 (Snellen equivalent) (extracted and modified from [4]).

Figure 3

Intermediate age-related macular degeneration. (a) Schematic cross-sectional illustration of the macula with an intermediate stage of the disease ((1) drusen; (2) atrophy of a cell of the retinal pigment epithelium; (3) hypertrophy or hyperplasia of a cell of the retinal pigment epithelium; (4) a normal cell of the retinal pigment epithelium). (b) Fluorescein angiography of the macula affected by an intermediate form of the disease (confluent soft drusen and pigmentary irregularities); in this eye, the best best-correct visual acuity was 20/50 (Snellen equivalent) (extracted and modified from [4]).

Figure 4

Advanced forms of age-related macular degeneration. (a) Autofluorescent retinography and (b) fluorescein angiography of two different cases of severe central geographic atrophy; in these eyes, the best-correct visual acuities were, respectively, 20/125 and 20/160 (Snellen equivalent). (c) Early and (d) late fluorescein angiograms of two different cases of subfoveal choroidal neovascularization; in both these eyes, the best-correct visual acuity was 20/200 (Snellen equivalent).