Vitamin D May Play Key Role in Preventing Macular Degeneration

 University at Buffalo research shows women with two risk alleles and low D status are more likely to have the disease

Newswise, August 31, 2015– Vitamin D has been studied extensively in relation to bone health as well as cancer. Now, a team led by a researcher at the University at Buffalo has discovered that vitamin D may play a significant role in eye health, specifically in the possible prevention of age-related macular degeneration, or AMD, among women who are more genetically prone to developing the sight-damaging disease.

In a paper published today (Aug. 27) in JAMA Ophthalmology online, Amy Millen, associate professor of epidemiology and environmental health in UB’s School of Public Health and Health Professions, and her team found that women who are deficient in vitamin D and have a specific high-risk genotype are 6.7 times more likely to develop AMD than women with sufficient vitamin D status and no high risk genotype.

“Most people have heard that you should eat carrots to help your vision. However, there appear to be many other ways that adequate nutrition can support eye health. Having adequate vitamin D status may be one of them,” says Millen, PhD, the study’s lead author. 

“This is not a study that can, alone, prove a causal association, but it does suggest that if you’re at high genetic risk for AMD, having a sufficient vitamin D status might help reduce your risk.”

“To our knowledge, this is the first study that’s looked at the interaction between genetic risk and vitamin D status in the context of age-related eye disease,” adds Millen.

Macular degeneration is characterized by the deterioration of the macula, a small part of the central retina where the eye’s photoreceptors (rods and cones) are most highly concentrated. 

The leading cause of legal blindness, macular degeneration affects more than 10 million Americans — more than cataracts and glaucoma combined — according to the American Macular Degeneration Foundation. The disease affects a person’s central vision, which is needed for common tasks such as reading and driving. The effect is similar to that of a rain drop on the center of a camera lens.

Researchers analyzed data compiled on 1,230 women ages 54 to 74 who participated in the Carotenoids in Age-related Eye Disease Study (CAREDS), which is an ancillary study of the Women’s Health Initiative (WHI) Observational Study (OS). 

The WHI OS is a major National Institutes of Health-funded research program aimed at addressing the most common causes of death, disability and poor quality of life in postmenopausal women. UB is one of 40 WHI centers nationally. 

CAREDS was conducted among participants at three of the centers: University of Wisconsin (Madison), the University of Iowa (Iowa City) and the Kaiser Center for Health Research (Portland, Oregon).

Researchers were able to determine participants’ vitamin D status by analyzing serum samples for a vitamin D biomarker, 25-hydroxyvitamin D [25(OH)D], which provided a glimpse into vitamin D intake through all sources: diet, supplements and sunlight.

Human skin can synthesize vitamin D when exposed to ultraviolet light, Millen explains. However, for many people, 15 to 30 minutes a day with 10 percent of their skin exposed might be sufficient. 

In winter months, when there is a lower solar angle, sun exposure may not be not sufficient to maintain blood level for people who live north of a line from about Washington, D.C., to Los Angeles. 

At these times and locations, dietary intake may be needed. Dietary sources of vitamin D include fortified foods such as milk and foods that naturally contain vitamin D such as fatty fish like salmon and mackerel.

“Macular degeneration has been found to be strongly associated with genetic risk,” Millen says. 

Among many genes linked to AMD, one of the strongest is a specific genetic variant (Y402H) in the complement factor H gene, called CFH for short. This gene codes for the CFH protein that is involved in the body’s immune response to destroy bacteria and viruses.

Inflammation is believed to be involved in the development of macular degeneration.

“People who have early stage AMD develop drusen, lipid and protein deposits that build up in the eye. Your body sees this drusen as a foreign substance and attacks it, in part via the complement cascade response,” explains Millen. 

“CFH is one of the proteins involved in this response. We see more AMD in people who have certain variants in the gene which encodes a form of this CFH protein that is associated with a more aggressive immune response.”

Vitamin D shows promise for protecting against macular degeneration because of its anti-inflammatory and antiangiogenic properties; antiangiogenic refers to slowing the growth of new blood vessels, often seen in late stages of AMD.

“Our thinking was, if a person’s vitamin D status is better, would it reduce the immune response to drusen? We wanted to understand if the association between vitamin D and AMD differed depending on a person’s genetic risk for AMD,” says Millen. 

“Our study suggests that being deficient for vitamin D may increase one’s risk for AMD, and that this increased risk may be most profound in those with the highest genetic risk for this specific variant in the CFH protein.”

The study results, however, shouldn’t prompt people to run to the nearest grocery store to purchase vitamin D supplements.

“Our message is not that achieving really high levels of vitamin D are good for the eye, but that having deficient vitamin D levels may be unhealthy for your eyes,” Millen says.

Although the odds of having AMD was higher in women who were deficient for vitamin D, with 25(OH)D levels below 12 ng/mL (30 nmol/L), increasing vitamin D levels beyond 12 ng/mL did not further lower the odds of AMD to any meaningful extent, she explains.

“This study supports a role for vitamin D in eye health. That’s significant because when the Institute of Medicine’s report on the dietary reference intakes for vitamin D and calcium were released in 2011, the committee could only make conclusions about D related to bone health,” says Millen. 

“There wasn’t enough evidence at that time to make any recommendation based on D status and other outcomes beyond bone health.”

Millen’s co-authors on the paper, titled “Association between vitamin D status and age-related macular degeneration by genetic risk,” include researchers from the University of Wisconsin-Madison, University of Iowa, Case Western Reserve University, Kaiser Permanente Center for Health Research and Fred Hutchinson Cancer Research Center. The study was funded by the National Eye Institute of the National Institutes of Health.

The Amazing Adaptability of the Brain’s Vision Center

Researchers uncover for the first time how and when the visual cortex of blind children adapts to respond to spoken language, sound, music 

Newswise, August 19, 2015 — By early childhood, the sight regions of a blind person’s brain respond to sound, especially spoken language, a Johns Hopkins University neuroscientist has found.

The results, published this week in The Journal of Neuroscience, suggest that a young, developing brain has a striking capacity for functional adaptation.

“The traditional view is that cortical function is rigidly constrained by evolution. We found in childhood, the human cortex is remarkably flexible,” said Johns Hopkins cognitive neuroscientist Marina Bedny, who conducted the research while at Massachusetts Institute of Technology. “And experience has a much bigger role in shaping the brain than we thought.”

Bedny, an assistant professor in the Department of Psychological and Brain Sciences, studied 19 blind and 40 sighted children, ages 4 to 17, along with Massachusetts Institute of Technology cognitive scientists Hilary Richardson and Rebecca Saxe. 

All but one of the blind children were blind since birth.

They monitored the children’s brain activity with functional magnetic resonance imaging while the children listened to stories, music or the sound of someone speaking an unfamiliar language. 

The blind children’s vision portion of the brain, the left lateral occipital area, responded to spoken language, music and foreign speech — but most strongly to stories they could understand. In sighted children and sighted children wearing blindfolds, that same area of the brain didn’t respond.

The researchers concluded that blind children’s ‘visual’ cortex is involved in understanding language.

Working with individuals who are blind offers cognitive researchers an opportunity to discover how nature and nurture, or a person’s genes and their experience, sculpt brain function.

Though scientists have shown that occipital cortexes of congenitally blind adults can respond to language and sound, this study offers the first look at how and when the change in brain function occurs.

The team found the blind children’s occipital cortex response to stories reached adult levels by age 4. Because spoken language had colonized the brain’s visual region so early in the children’s development, the team realized the brain adaptation had nothing to do with a child’s proficiency in Braille. Scientists had previously guessed that brain plasticity for spoken language in blind people had something to do with Braille.

Blind children’s occipital reaction to the other sounds, music and foreign speech, did increase as they aged.

Bedny believes her findings could one day lead to improved therapies for people with brain damage. If someone had a damaged part of the brain, she said it could be possible to train another part of the brain do the damaged part’s work.

“Early in development, the human cortex can take on a strikingly wide range of functions,” Bedny said. “We should think of the brain like a computer, with a hard drive ready to be programmed and reprogrammed to do what we want.”

This research was supported by the David and Lucile Packard Foundation and the Harvard/MIT Joint Research Grants Program in Basic Neuroscience.

Scientists find the brain works to minimize loss of vision, other functions

Newswise, August 17, 2015 – A new study may have unlocked understanding of a mysterious part of the brain — with implications for neurodegenerative conditions such as Alzheimer’s. The results, published in Translational Vision Science & Technology (TVST), open up new areas of research in the pursuit of neuroprotective therapies.

Glaucoma is a neurodegenerative disease where patients lose seemingly random patches of vision in each eye. This random pattern of vision loss is in stark contrast to loss from a brain tumor or stroke, which causes both eyes to develop blind spots in the same location. Scientists have long thought that glaucoma’s progression is independent of – or uncontrolled by – the brain.

Last year, researchers found evidence that the progression of glaucoma is not random and that the brain may be involved after all. Specifically, they found patients with moderate to severe glaucoma maintained vision in one eye where it was lost in the other — like two puzzle pieces fitting together (a “Jigsaw Effect”). 

“This suggests some communication between the eyes must be going on and that can only happen in the brain,” explains the study’s lead author, William Eric Sponsel, MD, of the University of Texas at San Antonio, Department of Biomedical Engineering.

In the latest TVST paper, Refined Frequency Doubling Perimetry Analysis Reaffirms Central Nervous System Control of Chronic Glaucomatous Neurodegeneration, Sponsel and his research team found that the Jigsaw Effect begins at the earliest stages of glaucoma and discovered clues as to which part of the brain is responsible for optimizing vision in the face of glaucoma’s slow destruction of sight.

However, these findings, which challenge longstanding assumptions about glaucoma, have been met with skepticism. Other glaucoma experts challenged the results in a letter to the TVST editor. 

“If the brain controls the distribution of vision loss in glaucoma, then a patient’s vision with their two eyes should be better than if you simply ‘mix and match’ the vision of right and left eyes from different patients,” explained letter co-author Paul Artes, PhD, of Plymouth University, Department of Eye and Visual Sciences. Along with co-author Jonathan Denniss, PhD, University of Nottingham, Visual Neuroscience Group, their letter analyzed a new cohort of glaucoma patients in which “that’s essentially what we did. And we did not find any visual advantage in a patient’s own eyes versus the combined vision in eyes from different patients; indeed we found the opposite effect.”

Sponsel and co-authors responded to the letter to the editor with their own. 

“Our analysis of the data [Artes and Denniss] introduced demonstrated conclusively that the ‘Jigsaw Effect’ was indisputably present in patients we had never even seen. Moreover, we were able to confirm that the alternative analytical method they proposed could not reliably detect very obvious computer-generated complementary visual field pairs,” like a left and right eye that could only see opposite halves of their normal field of vision, says Sponsel.

 “The problem with their approach was their assumption that a single brain could somehow combine information from the eyes of different human beings. We studied individual people with naturally paired eyeballs connected to a single brain.”

The key to finding where the brain coordinates vision loss was found in small-scale, arc-shaped patterns of vision displayed by patients. Co-author Ted Maddess, PhD, of the Australian National University, Center of Excellence in Vision Science, explains that these patterns mimic structures found at the very back of the brain, known as ocular dominance columns. While their function is not completely understood, what is known is that some ocular dominance columns are associated with the left eye and other columns with the right.

The new paper suggests that the narrow spaces between ocular dominance columns associated with the left and right eye are where the brain coordinates each eye’s working field of vision. Depending on what the brain needs, those narrow spaces can function with either eye “much like a bilingual person living near the border of two countries,” explains Sponsel.

The progression of Alzheimer’s and Parkinson’s diseases, which have neurodegenerative biology similar to glaucoma, may also be actively mediated by the brain. 

“Our work has illustrated that the brain will not let us lose control of the same function on both sides of the brain if that can be avoided. It seems likely that the same kind of protective mechanism will be at work with other neurodegenerative disorders,” he says.

The investigative team believes that if the brain regulates neurodegeneration – that if the brain controls how it loses control – then researchers will now be able to look into largely unexplored regulatory processes for opportunities to slow or stop the progression of these diseases.

“We’ve opened up this beautiful new world; there is so much to discover here,” says Sponsel.

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The ARVO journal Translational Vision Science & Technology, is an online only, peer-reviewed journal emphasizing multidisciplinary research that bridges the gap between basic research and clinical care, available at www.tvstjournal.org.

The Association for Research in Vision and Ophthalmology (ARVO) is the largest eye and vision research organization in the world. Members include nearly 12,000 eye and vision researchers from over 75 countries. ARVO advances research worldwide into understanding the visual system and preventing, treating and curing its disorders.