Immunopathological aspects of age-related macular degeneration

Abstract

Age-related macular degeneration (AMD) represents a leading cause of blindness worldwide. While the clinical and histopathological aspects of AMD are well characterized, its etiology and pathogenesis remain unclear. Recent findings suggest a role for immunologic processes in AMD pathogenesis, including the age-related generation of extracellular deposits inside the Brusch membrane and beneath the retinal pigment epithelium, recruitment of macrophages for clearance of these deposits, complement activation, recruitment of tissue-destructive macrophages, microglial activation and accumulation, and proinflammatory effects of chronic inflammation by Chlamydia pneumoniae. This review discusses the evidence for the role of inflammation in human AMD and in animal models of AMD.

Fig. 1

Fundoscopic and histologic representations of AMD and uveitis. a Fundoscopy of a human eye with AMD. Many drusen (arrow) and regions of RPE atrophy (asterisk) are visible by fundoscopy in a patient with dry AMD. b Photomicrograph of a human retina with wet AMD. Photoreceptor cells and most RPE (arrowhead) are replaced by a thick layer of fibrovascular tissue (asterisk) including small neovascular lumens (arrows). Ganglion cell layer, GC; photoreceptor layer, PR; RPE layer, RPE; and Bruch membrane, BM. (H & E, original magnification ×100). c Photomicrograph of a Cx3cr1^−/−/Ccl2^−/− mouse retina, a model for AMD. Choroidal neovascularization (arrows) and photoreceptor lesions (asterisk) are observed. Ganglion cell layer, GC; inner plexiform layer, IPL; inner nuclear layer, INL; outer plexiform layer, OPL; outer nuclear layer, ONL; photoreceptor layer, PR; and RPE layer, RPE. (H & E, original magnification ×200). d Fundoscopy of a human uveitic eye. Multiple large subretinal infiltrates (arrows) are visible by fundoscopy in a patient with Vogt–Koyanagi–Harada syndrome. e Photomicrograph of a human retina with uveitis. Massive inflammatory cellular infiltration (arrows) is seen in the edematous retina (R) and a thickened choroid (C) of a patient with sympathetic ophthalmia. (H & E, original magnification ×100). f Photomicrograph of a B10A mouse retina with experimental autoimmune uveitis. Focal retinal outer layer destruction (asterisk), retinal folds (arrow), and retinal and choroidal inflammatory cells are visible. (H & E, original magnification ×200)