Available now: Open-access interviews with experts on the COVID-19 pandemic: epidemiology, virus biology and possible vaccines and treatmentsView All
Harvard Medical School, USA
Age-related macular degeneration (AMD), the leading cause of vision loss in the US, is on the rise due to the rapidly aging population. AMD targets the macula, which is the very small area of the retina that is responsible for central vision. The prevalence of AMD rises with age, so... read morethat by age 74 about 2% will have AMD and this rises to close to 15% by the age of 80. There are two forms of advanced AMD: wet (or exudative) and geographic atrophy (GA) (or day) AMD.
In wet AMD, abnormal blood vessels grow from the choriocapillaris through Bruch’s membrane into the retinal space- either under or through the retinal pigment epithelium (RPE). These vessels leak fluid and blood that disrupt the fragile architecture of the retina. When the new vessels grow in the region of the macular there is a loss of central vision. The introduction of anti-VEGF therapies in 2006 revolutionized the treatment of wet AMD, not only stabilizing its progress but also often leading to improved vision. While VEGF induces both angiogenesis and permeability, it is the anti-permeability effects of VEGF neutralization that are believed to be at the heart of its efficacy.
Dry AMD is characterized by the death of the RPE, the ensuing atrophy of the choriocapillaris and degeneration of the photoreceptor cells. There is currently no treatment for the advanced form of dry AMD, referred to as geographic atrophy. However, there are significant on-going efforts aimed at transplantation of the RPE with the hope of slowing or reversing the disease progression.
While the pathogenesis of AMD is not understood, findings over the past decade point to a role for chronic inflammation in the development of AMD. While there had been speculation by some that inflammation contributed to AMD, the finding of polymorphisms in various components of the complement pathway (particularly complement factor H) associated with higher risk for the pathology provided conclusive support. In spite of this insight, the precise contribution of inflammation is has not been elucidated.
The initial site of AMD pathogenesis is generally held to be the RPE. There are some who speculate that the disease may begin with photoreceptors or the choroid but evidence to support these as sites is minimal. While the presence of drusen is a hallmark of AMD, whether they play a role in the cause or effect of AMD is unclear. That said, most preclinical research is based on the hypothesis that AMD initiates with damage to the RPE. This assumption, coupled with genetic evidence for the contribution of inflammation to AMD, has led to a range of studies examining various aspects of inflammation including the involvement of macrophages/microglia and the role of inflammasome activation.
This series of presentations on AMD will include researchers and physician-scientists who are the leaders in their respective areas of AMD. Together, these speakers will cover our current knowledge and will provide insights into future directions.