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Paradigm of Susceptibility Genes in AMD and PCV

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Advances in Vision Research, Volume I

Part of the book series: Essentials in Ophthalmology ((ESSENTIALS))

Abstract

Age-related macular degeneration (AMD) is a neurodegenerative disease and a cause of progressive blindness effecting millions of elderly people (over age of 50 years) worldwide. It is a complex disease with differing epidemiology, clinical features, pathogenesis, treatment, and genetics in Europeans and Asians. Specifically, polypoidal choroidal vasculopathy (PCV), a subtype of neovascular AMD, is more common in Asians compared to Western counterparts and exhibits different characteristics in all of these features.

Since the first genome-wide association study (GWAS) in 2005, which led to the discovery of the complement factor H (CFH) gene as a major risk factor in AMD, a number of studies have reported association of genes in the complement pathway, indicating its key role in AMD susceptibility. In addition, common genetic variants associated with AMD have been extensively investigated by two consortia, the International AMD Gene Consortium and the Genetics of AMD in Asians (GAMA), where GWAS has been undertaken on both large European and Asian AMD cohorts, respectively. These studies reported different genetic risk factors associated with AMD in Europeans and Asians.

In the case of PCV, it has been shown that a number of common genetic risk factors are shared with neovascular AMD but have different clinical presentations, perhaps indicating involvement of differential biological mechanisms, for which separate GWAS studies in large PCV cohorts are warranted.

Currently the standard treatment for neovascular AMD, as well as more recently for PCV, is anti-vascular endothelial growth factor (anti-VEGF) injections. However, different treatment outcomes have been reported and the reason for this is likely to be partly explained by genetic variants. While much progress has already been made, there are still many challenges that remain in understanding both AMD and PCV, in terms of early diagnosis, disease prediction, and personalized treatment approaches.

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Acknowledgments

This study was supported through the National Health and Medical Research Council of Australia (NHMRC) project grant 1008979 and Senior Research Fellowship 1028444 (PNB). A Melbourne International research Scholarship and Melbourne International fee remission scholarship from the University of Melbourne (MR). The Centre for Eye Research Australia (CERA) receives operational infrastructure support from the Victorian Government.

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  1. Centre for Eye Research Australia, Department of Surgery (Ophthalmology), University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia

    Moeen Riaz & Paul N. Baird

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  1. National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA

    Gyan Prakash

  2. Tokyo Medical Center, National Institute of Sensory Organs, Tokyo, Japan

    Takeshi Iwata

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Riaz, M., Baird, P.N. (2017). Paradigm of Susceptibility Genes in AMD and PCV. In: Prakash, G., Iwata, T. (eds) Advances in Vision Research, Volume I. Essentials in Ophthalmology. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56511-6_14

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