Macular Degeneration—An Addendum

Abstract

In the last decade there has been an increasing focus on developing new treatments for age-related macular degeneration because of the burgeoning aging population in the Western world. Many attempts have been made to find genes important to the onset of macular degeneration in the hope that we will understand the biological mechanisms and pathways that trigger the disease so that we can develop the most effective intervention strategies. Linkage and candidate gene studies have indicated that macular degeneration is a multigenic disease. In chapter 2,Wang et al. describe the evidence for a possible role of the ABCA-4, a retina-specific ATP-binding cassette transporter protein and the Apo-E gene, which encodes for a lipoprotein that maintains normal levels of cholesterol, as two genes that are risk factors for AMDR when they are dysfunctional. A recent review provides more details of the linkage studies that suggest a role for these genes and lists others that have been proposed (1). ABCA-4 is clearly involved in the early onset Stargardt’s disease but has a less clearly defined role in adult AMD. Different alleles of Apo-E can confer risk for or protection from AMD but the effect is relatively minor. Hemicentin-1, a gene on chromosome 1 encoding an extracellular matrix protein, was previously thought to be important in AMD but is now viewed as a marker for real AMD risk genes in the same region of chromosome 1. The linkage and candidate gene studies have resulted in our understanding of how the dysfunction of some genes may be risk factors for the pathogenesis of AMD. However, these do not account for a significant number of the diseased cases or provide a clear indication of the causes of AMD.