Abstract
Age-related macular degeneration (AMD) specifically affects the macular region of the central retina,where both ganglion cells and cones are present at very high densities. At the approximate centre of the macula is the fovea centralis a small depression in the retinal surface overlying the peak concentration of cone pho toreceptors. It is the very high density of cones in the macular region, along with their synaptic relationships with a population of midget ganglion cells, which provide the anatomical bases for our capacity to resolve fine detail (see Chap. 1). Lesions resulting from AMD are often small, but have a high impact on vision because of the number of cells, particularly ganglion cells, affected. Lesions of the dimensions common in AMD but occurring in more peripheral parts of the retina have little, if any, impact on visual acuity or quality of life, because only a relatively small number of cells is affected. Paradoxically, while the macula has the highest concentration of receptors and neuronal elements in the retina, it has a limited vascular supply. During development, blood vessels are inhibited from entering the incipient fovea, even though initially no anatomical specialization is apparent (Provis et al. 2000). The foveal depression forms within a specified avascular region that blood vessels and astrocytes do not enter at any stage of development. Reduction in vascular density is a specialization associated with high-acuity areas in other species, including the cat (Chan-Ling et al. 1990) and prosimian primates (Woollard 1927; Rohen and Castenholtz 1967; Wolin and Massopust 1970), which have an area centralis rather than the fovea centralis present in most simian primates including humans (Provis et al. 1998). Thus it appears that a reduction in vascularity of the high-acuity area (area or fovea centralis) is a specialization associated with improved visual acuity in a variety of species (Provis et al. 2000; Sandercoe et al. 2003). Such a specializa-tion ensures that light reaching the foveal cone mosaic is not diffracted by vascular structures lying in the light path, ensuring optimal quality of the visual information being relayed to the brain. The high density of cones in the foveal cone mosaic is the fundamental substrate of high visual acuity.Amongst primates high cone density has evolved hand-in-hand with a fovea centralis, and human foveae have amongst the highest densities of cones (Packer et al. 1989; Curcio and Allen 1990). However, photoreceptors are oxygen-hungry, and their very high density within a region where oxygen supplylines are reduced is an adaptation with evident physiological limitations. While such limitations may not be evident in young, healthy individuals, insurance and evolution must each cope with the fact that risk goes up with time (Jones 1999). The price of high-acuity vision during the early years of life, therefore, may be the risk of photoreceptor loss later in life or vulnerability to degenerative disease. Macular degeneration occurs in two forms, an atrophic lesion (dry),originally described by Nettleship (1884) and Haab (1885), and a neovascular lesion (wet) originally described by Pagenstecher and Genth (1875). A century later, Gass (1973) suggested that the atrophic and neovascular lesions may be manifestations of the same disease process, although the relationship between their etiologies remains to be established. The term age-related macular degeneration, has been adopted to include both forms. The histological appearance of the normal macula, incipent forms and end-stage lesions are illustrated in Fig. 2.1. It would appear, therefore, that in the adult macula there is a critical relationship between limited blood supply and high metabolic demand (Penfold et al. 2001a, 2001b). Even minor perturbations of circulation, for example in incipient vascular disease, may lead to metabolic stress in foveal neurons and/or glia. Such perturbations and the resultant stress may generate signals that induce the neovascular changes associated with wet AMD (Figs. 2.1E and 2.5). Chronic failure of choroidal vascular supply at the macula may result in atrophy or dry AMD (Figs. 2.1F and 2.7) usually considered to be the natural end-stage of the disease.
Original language | English |
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Title of host publication | Macular Degeneration |
Publisher | Springer Berlin Heidelberg |
Pages | 25-44 |
Number of pages | 20 |
ISBN (Print) | 3540200584, 9783540200581 |
DOIs | |
Publication status | Published - 2005 |