Age-related macular degeneration (AMD) is a progressive, complex disease, representing the most common cause of legal blindness in the developed world. In the United States alone, the prevalence of any type of AMD in individuals over the age of 40 is conservatively about 6.5%, or 7.2 million [1
]. Risk factors for AMD include age, smoking, and a number of genetic polymorphisms.
Early stages of AMD are clinically characterized by changes in retinal pigment epithelium (RPE) pigmentation and accumulation of drusen, extracellular deposits beneath the RPE. In some patients, AMD progresses to severe retinal atrophy and/or the pathologic growth of blood vessels from the choroid into the retina, a destructive process called choroidal neovascularization (CNV) (Figure ). For reasons not completely understood, these events are predominantly localized to the macula, a specialized region of the retina that performs the crucial task of delivering sharp, central vision. Loss of macular photoreceptor cells results in inability to read, drive, or recognize faces. Several biological processes have been implicated in the pathogenesis of AMD, including complement-activation [2
], inflammation [3
], and oxidative stress [4
Figure 1 Structural features of eyes with AMD. (A) Schematic of human eye with the macular region indicated by the bracket. (B-E) Histological sections of eyes from individuals with normal retina (B); drusen (asterisks) beneath the RPE, a sign of early stage AMD (more ...)
While the last decade has seen great progress in understanding the pathophysiology of AMD, the molecular changes that occur in eyes with AMD are still poorly understood. The study of AMD is complicated by the limitations of animal models (for example, apart from primates, mammals lack a specialized macula), necessitating the use of human tissue. Anti-angiogenic drugs have been used to suppress CNV; however, no treatments are currently available to halt AMD prior to irreversible retinal damage, although dietary modulation may provide some benefit [5
]. Identification of potential therapies may be facilitated by high-throughput systems biological analyses, particularly at the proteome and transcriptome levels.
Previous studies assessing mRNA levels in normal human retina, RPE, and choroid revealed tissue-specific molecular signatures [7
] and differences between macular and extramacular transcript expression [9
]. However, systematic transcriptional profiling had not been performed on AMD affected tissues, and the overall molecular phenotypes of AMD have not been thoroughly examined.
In the current issue of Genome Medicine
, Newman and colleagues address this gap. The authors compared gene expression of 37 AMD eyes (divided into categories based on disease phenotype) with 31 normal eyes [14
]. Expression profiling was performed for both the neural retina and the combined RPE/choroid layers of the eye using an oligonucleotide microarray platform. These experiments uncovered distinct molecular signatures for each assigned AMD class, termed disease modules, as well as a set of differentially regulated genes shared by all classes. By overlapping disease modules with existing protein association data, Newman et al
. constructed interaction networks (interactomes) for AMD in RPE/choroid and retina.