Glaucoma's unique protein expression could enhance diagnosis and treatment

An eye under pressure appears to express a unique set of proteins that physicians hope will one day help them better diagnose and treat glaucoma.

Glaucoma, the second leading cause of blindness worldwide, tends to progress silently until decreased vision indicates trouble, said Dr. Kathryn Bollinger, Medical College of Georgia clinician-scientist specializing in glaucoma.

But inside fluid-filled eyeballs, a changing protein profile -- 30 with significant increases and 17 with significant decreases identified among hundreds of proteins present -- appears to also give a heads-up, Bollinger reported during the Association for Research in Vision and Ophthalmology Annual Meeting April 30-May 6. The MCG ophthalmologist received the 2010 ARVO/Alcon Early Career Clinician-Scientist Research Award for the study.

With glaucoma, elevated pressures inside the eyeball stress the optic nerve and nerve arms -- called axons ? that reach out to communicate with the brain. Over time, increased pressure can kill nerve cells and axons and decrease vision. "At this point, we don't have a regenerative strategy," Bollinger said.

The pressure results from an imbalance in fluid production and loss. In a healthy eye, the fluid, called the aqueous humor, moves continually from the back to the front of the eye where it exits ? mostly via a natural tract between the iris and cornea ? first into spongy tissue near the cornea's base called the trabecular meshwork then into the venous system and back into the body.

In open-angle glaucoma, the most common type in this country, the tract remains open but fluid still backs up and scientists suspect changes in the permeability of the trabecular meshwork may be to blame. Topical glaucoma treatments work by reducing fluid production or increasing outflow through a secondary drainage system, also near the front of the eye. Ophthalmologists such as Bollinger can also create a new pathway surgically if needed.

To get a better picture of what happens to the trabecular meshwork, Bollinger examined tissues from the outflow tracts and trabecular meshwork of patients with and without glaucoma. She added TGF-?, a protein and inflammatory element known as a cytokine that is consistently found at high levels in patients with open-angle glaucoma. After comparing treated and untreated tissue, she found that TGF-? resulted in a similarly unique protein pattern. Current therapies don't target TGF-? or its effects in the trabecular meshwork.

Next steps include identifying additional proteins expressed in glaucoma, determining the impact of the unique protein profile on the trabecular meshwork and clarifyingTGF-?'s normal role inside the eye, Bollinger said.

Risk factors for glaucoma include age, a family history and black and Asian ethnicity.


Link: http://www.mcg.edu

Artistic Endeavour and Schizophrenia: The Connection found in Edinburgh

Salvador Dali's mental disorders were also the key to his creativity. (Image: Philippe Halsman)

We are all familiar with the stereotype view of the tortured artist. Salvador Dali's various disorders and Sylvia Plath's depression, spring to mind. Now new research seems to show why: a genetic mutation linked to psychosis and schizophrenia also influences creativity.

The finding could help to explain why mutations that increase a person's risk of developing mental illnesses such as schizophrenia and bipolar syndrome have been preserved, even preferred, during human evolution, says Szabolcs Kéri, a researcher at Semmelweis University in Budapest, Hungary, who carried out the study.

Kéri examined a gene involved in brain development called neuregulin 1, which previous studies have linked to a slightly increased risk of schizophrenia. Moreover, a single DNA letter mutation that affects how much of the neuregulin 1 protein is made in the brain has been linked to psychosis, poor memory and sensitivity to criticism.

About 50 per cent of healthy Europeans have one copy of this mutation, while 15 per cent possess two copies.

Creative thinking

To determine how these variations affect creativity, Kéri genotyped 200 adults who responded to adverts, seeking creative and accomplished volunteers. He also gave the volunteers two tests of creative thinking, and devised an objective score of their creative achievements, such as filing a patent or writing a book.

People with two copies of the neuregulin 1 mutation – about 12 per cent of the study participants – tended to score notably higher on these measures of creativity, compared with other volunteers with one or no copy of the mutation. Those with one copy were also judged to be more creative, on average, than volunteers without the mutation. All told, the mutation explained between 3 and 8 per cent of the differences in creativity, Kéri says.

Exactly how neuregulin 1 affects creativity isn't clear. Volunteers with two copies of the mutation were no more likely than others to possess so-called schizotypal traits, such as paranoia, odd speech patterns and inappropriate emotions. This would suggest that the mutation's connection to mental illness does not entirely explain its link to creativity, Kéri says.

Dampening the brain

Rather, Kéri speculates that the mutation dampens a brain region that reins in mood and behaviour, called the prefrontal cortex. This change could unleash creative potential in some people and psychotic delusions in others.

Intelligence could be one factor that determines whether the neuregulin 1 mutation boosts creativity or contributes to psychosis. Kéri's volunteers tended to be smarter than average. In contrast, another study of families with a history of schizophrenia found that the same mutation was associated with lower intelligence and psychotic symptoms.

"My clinical experience is that high-IQ people with psychosis have more intellectual capacity to deal with psychotic experiences," Kéri says. "It's not enough to experience those feelings, you have to communicate them."

Intelligence's influence

Jeremy Hall, a geneticist at the University of Edinburgh in the UK who uncovered the link between the neuregulin 1 mutation and psychosis, agrees that the gene's effects are probably influenced by cognitive factors such as intelligence.

This doesn't mean that psychosis and creativity are the same, though. "There's always been this slightly romantic idea that madness and genius are the flipside to the same coin. How much is that true? Madness is often madness and doesn't have as much genetic association with intelligence," Hall says.

Bernard Crespi, a behavioural geneticist at Simon Fraser University in Burnaby, British Columbia, Canada, is holding his applause for now. "This is a very interesting study with remarkably strong results, though it must be replicated in an independent population before the results can be accepted with confidence," he says.