Partners in Research Supports Visionary Scientists

Posted in GUMC Stories  |  Tagged aging, biomedical research, macular degeneration, ophthalmology, Partners in Research

(December 14, 2019) — Research is a chicken-and-egg phenomenon. One thing leads to another. But without investigational funding there is no chicken. And no egg. 

So says Nady Golestaneh, PhD, MSc, adding that she would not be where she is today in her quest to prevent a common blindness in the elderly without small grants that provided stepwise surges in her studies.

“Even the greatest idea will die if research isn’t supported,” says Golestaneh, an associate professor in GUMC’s departments of ophthalmology, neurology, and biochemistry and molecular & cellular biology and director of research in the department of ophthalmology.

In March, Golestaneh successfully competed for a $1.9 million National Institutes of Health (NIH) R01 award, which gives an investigator up to five years of independent support and time in order to complete a project and publish results. Good work often leads to another such sustaining federal grant.

“It’s the chicken and egg again,” says Golestaneh, who also serves as president of Georgetown Women In Medicine (GWIM). “Without preliminary data and publications, you could never get an R01, but without funds, you can’t obtain the data that is needed.” 

What was critical to her success were the grants GUMC awarded to Golestaneh, starting with a $25,000 award from Partners in Research in 2011 and followed by a $100,000 Research Breakthrough Award in 2018, also from Partners in Research. With additional support from a Dean’s Pilot Grant in 2012, a $120,000 award from the Bright Focus Foundation in 2014, and $50,000 awards from the Prevention of Blindness Society in 2014, 2016 and 2018, Golestaneh collected the preliminary data she needed to successfully compete for an R01 in the department of ophthalmology, a purely clinical department prior to her joining. 

The Eye: A Vision of Beauty

Golestaneh has always been fascinated with vision. Her PhD work is on the retina, and she worked on the development of eye lenses at the NIH during a postdoc and again during another postdoc at Johns Hopkins University, where she worked on retinal degeneration. “The eye is such a small organ, but it is very independent — just magnificent.” 

Golestaneh is determined to channel the support she has and is receiving into reducing the burden of vision loss and blindness caused by age-related macular degeneration (AMD), a condition characterized by blurred or loss of vision in the center of the visual field due to a damaged macula — a structure that helps with high acuity vision — in the center of the retina. According to the NIH, about 11 million individuals are affected by macular degeneration in the U.S., with a global prevalence of 170 million. The condition often leads to irreversible blindness and is the leading cause of vision loss in the U.S., affecting more than 10% of the population aged 65-74 and more than 25% of the population older than 74 years.

Most people develop “dry” AMD before it transforms into the “wet” form. The dry form, which Golestaneh studies and which affects 90% of the patient population, is caused by deposits of lipids and proteins in the retina, which ultimately will lead to degeneration of photoreceptors. The wet form is the advanced version in which new blood cells form in the retina, destroying it. “So many people lose their vision and remain hopeless,” Golestaneh says. “There is no good treatment recourse for the dry form of AMD.”

Research Leads to Treatment Strategy

Working with her lab colleagues, Golestaneh has searched for the origins of dry AMD by comparing retinas donated from donor eyes with unaffected retinas. 

“I have observed a lot of differences, and one of the most important is the ability a normal retina has to sense and eliminate waste,” she says. “That is missing in the retina of patients with dry AMD.” This insight was completely new, and she needed proof of her findings in animal models before she could publish.

Using human stem cells to create in vitro and in vivo models of dry AMD, Golestaneh has defined several pathways involved in the disease, including the energy sensor AMPK which, when inactive, leads to protein buildup in cells, SIRT1, which activates waste clearing, and PGC-1a, which is responsible for mitochondrial biogenesis. These observations were published in 2018.

Furthermore, Golestaneh has identified several proteins in these pathways that may be candidates for drug treatment. She is currently testing four potential molecules on her unique mouse model of human dry AMD. “If we can stop dry macular degeneration, the advanced wet form may not develop,” she says.

Without the support she received from Georgetown, Golestaneh says she would not be able to “pay it forward,” like she wants to do in treatment of macular degeneration. “It is a visionary thing to invest in research,” she says. “And it is vision that I want to give back.”

Renee Twombly
GUMC Communications