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Dry AMD requires broad, systems biology approach leveraging big data, multiple disciplines

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Posted August 1, 2019
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A large-scale, collaborative, systems biology approach is needed to expedite the discovery of treatments for dry age-related macular degeneration (AMD) – a leading cause of blindness among people 65 and older for which is there is no treatment— according to a report by a working group of scientists appointed by the National Advisory Eye Council (NAEC). The NAEC is a 12-member panel that guides the National Eye Institute (NEI), part of the National Institutes of Health. The NAEC charged the working group to assess the state of research on dry AMD and to propose directions for future research.

“The working group thoroughly assessed what is known about dry AMD pathobiology, and the recommendations will be informative for considering future NEI research priorities to align with promising pathways for discovering therapeutic targets,” said NEI Director, Paul A. Sieving, M.D., Ph.D.

Dry AMD is accompanied by drusen deposits and the degeneration of the retinal pigment epithelium (RPE) and subsequent loss of the light-sensing photoreceptors and the capillary network called the choriocapillaris. Image credit: NEI

In the United States alone, an estimated 11 million people have AMD, and the dry form, otherwise known as non-neovascular AMD, accounts for most cases. Less prevalent is the neovascular “wet” form of AMD, for which several treatment options are available. Wet AMD involves an overgrowth of new blood vessels within eye structures that typically leads to rapid and severe vision loss. The advent of anti-VEGF drugs aimed at preventing the growth of new blood vessels dramatically changed the prognosis for many patients with the disease.

By contrast, no therapies exist for dry AMD, which tends to progress more gradually, causing a slower decline in visual function.

Both forms of AMD involve a complex interplay of pathogenic factors, including genetics and lifestyle risk factors such as smoking. Research thus far has failed to decipher how these various factors interact in dry AMD and, according to the report, success in doing so would require a large-scale, collaborative and multidisciplinary approach.

“We propose that researchers utilize a systems biology approach, integrating the big data available from clinical registries and various fields of biology known as ‘omics’ to develop better models and ultimately treatments for patients with this blinding disease,” said report co-author Joan W. Miller, M.D., chair, Harvard Medical School Department of Ophthalmology, Boston.

“This approach would integrate basic, genomic, pre-clinical, medical, pharmacological, and clinical data into mathematical models of pathological processes at different stages of dry AMD in order to ask how relevant individual components act together within the living system,” Dr. Miller said.

Source: NIH

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