The molecular genetic basis of age-related macular degeneration: an overview

Abstract

Age-related macular degeneration (AMD) is a complex disorder of the eye and the third leading cause of blindness worldwide. With a multifactorial etiology, AMD results in progressive loss of central vision affecting the macular region of the eye in elderly. While the prevalence is relatively higher in the Caucasian populations, it has gradually become a major public health issue among the non-Caucasian populations (including Indians) as well due to senescence, rapidly changing demographics and life-style factors. Recent genome-wide association studies (GWAS) on large case-control cohorts have helped in mapping genes in the complement cascade that are involved in the regulation of innate immunity with AMD susceptibility. Genes involved with mitochondrial oxidative stress and extracellular matrix regulation also play a role in AMD pathogenesis. Majority of the associations observed in complement (CFH, CFB, C2 and C3) and other (ARMS2 and HTRA1) genes have been replicated in diverse populations worldwide. Gene-gene (CFH with ARMS2 and HTRA1) interactions and correlations with environmental traits (smoking and body mass index) have been established as significant covariates in AMD pathology. In this review, we have provided an overview on the underlying molecular genetic mechanisms in AMD worldwide and highlight the AMD-associated-candidate genes and their potential role in disease pathogenesis.

Cigarette Smoke-Related Hydroquinone Induces Filamentous Actin Reorganization and Heat Shock Protein 27 Phosphorylation through p38 and Extracellular Signal-Regulated Kinase 1/2 in Retinal Pigment Epithelium

“…[1][2][3][4] An estimated 13 million Americans have some degree of AMD and unless better preventive treatments emerge, this number is expected to climb and even reach epidemic proportions with the overall aging demographics. Although the cause of AMD has not yet been fully determined, this complex multifactorial disease clearly results from the interplay of multiple genetic and environmental risk factors 2,5 that lead to progressive destruction of retinal pigment epithelial (RPE) cells and photoreceptors and ultimately to vision loss.…”

Inflammation in Age-Related Macular Degeneration – Implications for Therapy

“…Polymorphisms in a number of complement genes (CFH, CFB, C2, and C3) increase the risk of AMD (Edwards. 2008, Katta et al 2009). However, there are many important questions remain to be answered.…”

“…In addition to environmental factors, clinical studies have found that the risk of AMD is also affected by genetic factors. Genes that are involved in AMD susceptibility fall into three categories: immune-related genes (CFH, CFB, C2, C3, C5, Cx3cr1, TLRs, IL-8, HLAs), mitochondrial and oxidative stress-related genes (ARMS2 and HTRA1) and extracellular matrix related genes (PRELP, LAMC1, LAMC2, LAMB3, FIBULIN2, and ITGB4) (Katta et al 2009). Importantly, the majority of the immune-related genes are related to the innate immunity, including the complement system (CFH, CFB, C2, C3 and C5) (Lotery andTrump.…”

Toll-like receptor 3 polymorphism is not associated with neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in the Chinese

“…Familial (Klaver et al, 1998;Smith and Mitchell, 1998) and twin studies (Klein et al, 1994;Meyers et al, 1995) implicated the role of genetic predisposition of AMD (Katta et al, 2009). Genome-wide association studies identified the complement factor H (CFH) gene on chromosome 1q32 as a susceptibility gene for AMD (Edwards et al, 2005;Klein et al, 2005).…”