Starving eye cells contribute to blindness in elders

March 14, 2016, University of Montreal

Age-related macular degeneration (AMD) is the leading cause of visual impairment in people over 50 in developed countries. Although this condition affects up to 20% of people between the ages of 65 and 75, what drives abnormal blood vessels to invade the retina is unknown. Researchers from Montreal and Boston now provide a new mechanism for that blinding retinal disease in a study just published in the prestigious scientific journal Nature Medicine.

"In a murine model of AMD, we found that the inability of photoreceptors - nerve cells that capture light and generate vision - to produce energy may drive abnormal blood vessels to invade the retina" said Jean-Sébastien Joyal, an intensive care pediatrician at mother-child research hospital CHU Sainte-Justine and professor in the Department of Pediatrics at the University of Montreal. "We also discovered that photoreceptors do not rely exclusively on glucose to produce energy as previously thought, but also use lipids as a fuel substrate (like the heart, for example)" he said.These findings debunk the scientific beliefs surrounding the cause of abnormal proliferation of blood vessels leading to blindness, and thus open new therapeutic avenues for retinal diseases such as AMD.

Compensating for energy deficiency

The retina is covered with photoreceptors, which thrive on oxygen and nutrients carried by the blood. The abnormal growth of blood vessels causes blindness in some retinal diseases. "In general, the scientific community agrees that proliferation of blood vessels occurs when the body attempts to compensate for oxygen deficiency. We now show that abnormal vessels may also grow to compensate for a lack of fuel or energy production, in a model of AMD," said Dr. Joyal.

Fat as energy substrate—a possible evolutionary advantage

The type of energy used also surprised the scientists in their study. "To our surprise, we found that photoreceptors also feed on fatty acids. It was previously believed that these specialized nerve cells, which are energy-intensive, rely primarily on glucose," said Dr. Joyal. The ability of photoreceptors to use different fuel sources to produce energy may provide an evolutionary advantage during feast and famines.

Plunged into darkness to boost energy consumption

The researchers suspected that dysregulated energy metabolism of photoreceptors might contribute to AMD. They used a murine model unable to use lipids efficiently and observed the presence of abnormal retinal blood vessels resembling AMD. These models developed a lot more retinal lesions when raised in darkness, which is known to increase the energy consumption of the retina. This evidence suggested a link between energy demands and vascular supply of the retina.

Lipid sensors control glucose uptake and energy production

When deprived of fatty acids, can photoreceptors use glucose instead? "Probably in normal , but paradoxically not in our lipid-uptake deficient model. These have elevated circulating blood levels of fatty acids. To explain this puzzling observation, we found the presence of lipid sensors on the surface of photoreceptors. We think these receptors help match available fuel substrate in circulation with the energy production of photoreceptors. When lipid sensors detect excess fatty acids in the blood, it considers the available lipid fuel to be sufficient and suppresses glucose absorption."

Dr. Joyal summarizes the situation as follows: "In lipid-uptake deficient models, photoreceptors end up being starved for both and glucose. Starved photoreceptors secrete signals that attract new in order to increase nutrient supply. By proliferating behind the retina however, these vessels cause a decline in eyesight, leading to blindness." So at the end of the day, what's the take-home message? "Well, there are three based on our in vivo findings", recaps Dr. Joyal. "AMD may be caused in part by an energy deficiency. Fat is also a source of for photoreceptors. And lipid sensors may control glucose entry in the retina."

Further work must be carried out to develop new therapy that will build on these discoveries with the aim of preventing, slowing down or reversing vision loss caused by retinal diseases such as AMD.

Explore further: Potential new approaches to treating eye diseases

More information: The article "Retinal lipid and glucose metabolism dictates angiogenesis through lipid sensor Ffar1" was published in the journal Nature Medicine on March 14, 2016. DOI: 10.1038/nm.4059

Related Stories

Potential new approaches to treating eye diseases

February 4, 2016
Potential new approaches to treating eye diseases such as age-related macular degeneration (AMD) are described in a new study, "IL-33 amplifies an innate immune response in the degenerating retina," in the February Journal ...

A new therapeutic target may prevent blindness in premature babies at risk of retinopathy

September 16, 2014
Possibility of developing new, more selective drugs to control the abnormal growth of blood vessels and prevent blindness including retinopathy of prematurity, a disorder that may result in retinal detachment due to abnormal ...

Patients with macular degeneration show improvement with high-dose statin treatment

February 4, 2016
Researchers at Massachusetts Eye and Ear/Harvard Medical School and the University of Crete have conducted a phase I/II clinical trial investigating the efficacy of statins (cholesterol-lowering medications) for the treatment ...

Specific protein essential for healthy eyes, study finds

January 7, 2013
Researchers at the Hebrew University of Jerusalem, in collaboration with researchers at the Salk Institute in California, have found for the first time that a specific protein is essential not only for maintaining a healthy ...

Finding hope in the dark

June 10, 2015
Advances in stem cell transplantation and gene therapy have been pioneered in vision research. An international team of researchers from Bristol, Toronto, Pittsburgh, Dallas and Montreal have identified a gene that could ...

Nerve cells and blood vessels in eye 'talk' to prevent disease, study finds

April 27, 2015
A new study from scientists at The Scripps Research Institute (TSRI) shows that nerve cells and blood vessels in the eye constantly "talk" to each other to maintain healthy blood flow and prevent disease.

Recommended for you

Researchers report vision-based neurotransmitter events for the first time

November 27, 2018
How does vision work, and what happens in the brain during the process? As simple as this question may sound, it has yet to be scientifically clarified. Dr. Valentin Riedl of the Technical University of Munich (TUM) and his ...

Minimally invasive retinal detachment has better outcomes, clinical trial findings

November 26, 2018
A minimally invasive treatment for retinal detachment gives patients sharper vision, less distortion and reduced side-effects, according to the findings of a randomized controlled trial performed at St. Michael's Hospital ...

Scientists combine technologies to view the retina in unprecedented detail

November 14, 2018
By combining two imaging modalities—adaptive optics and angiography—investigators at the National Eye Institute (NEI) can see live neurons, epithelial cells, and blood vessels deep in the eye's light-sensing retina. Resolving ...

Eyepatch with dissolvable needles used to treat eye disease

November 12, 2018
A team of researchers affiliated with several institutions in Singapore has developed an eyepatch with dissolvable needles for use in treating eye diseases. In their paper published in the journal Nature Communications, the ...

Calcifications in the eye increase risk for progression to advanced AMD by more than six times

November 8, 2018
Calcified nodules in the retina are associated with progression to late stages of age-related macular degeneration (AMD). Experts from Queen's University Belfast, working in partnership with the University of Alabama of Birmingham ...

Traditional glaucoma test can miss severity of disease

November 8, 2018
The most common tests for glaucoma can underestimate the severity of the condition by not detecting the presence of central vision loss, according to a new Columbia University study.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.