HTRA1 in Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a leading cause of severe visual impairment and irreversible blindness in most developed countries, affecting more than 50 million of elderly people worldwide. Current treatments, such as intravitreal injection of antiangiogenic agents, mitigate the effect of advanced AMD but cannot completely cure the disease. Comprehensive understanding of the AMD pathological mechanisms is important for the development of new therapies. Previously, we identified a single-nucleotide polymorphism (rs11200638) in the promoter region of the high temperature requirement factor A1 (HTRA1) gene on chromosome 10q26 to be associated with exudative AMD. In further biological studies, we have provided evidence that HTRA1 could be a potential disease-causing gene within the 10q26 locus. In this review, we summarize the pathology of AMD and the molecular function of the HtrA1 protein. Also evaluated are the genetic effects of HTRA1 polymorphism on AMD in different populations and interactions with other AMD-associated genes, especially with the complement factor H (CFH) gene, which was identified for nonexudative AMD. The biological roles of HtrA1 are exhaustively examined on its contribution to the multifactorial pathogenic mechanism of AMD. Although HtrA1 should play a part in AMD pathogenesis, a host of other genetic and environmental factors, known and unknown, is involved and warrants intensive future research.