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Out of the Darkness

Out of the Darkness

By Mandy Thoo

Researchers find that light therapy and saffron can protect us against the leading stealers of sight.

As we live longer our eyesight fails, leaving many of us helpless in the dark for years towards the end of our lives. In the fight against sight-stealers, scientists at the ARC Centre of Excellence in Vision Science are opening new fronts: fast, accurate and painless eye tests, slowing the advance of damaging eye diseases, and pioneering techniques that may one day actually reverse the loss of sight.

The greatest enemies of sight in the coming decades will be age-related macular degeneration (AMD) and diabetic retinopathy. Caused by genetics, age, bright lights and unhealthy living, these eye diseases already darken the world for millions of people and cost billions of dollars.

AMD is one of the world’s leading causes of blindness, affecting one in seven Australians over the age of 50 at a cost of $2.6 billion per year. By 2030 it will rob an estimated 1.77 million Australians of their ability to read, drive, see in colour, recognise faces and perform activities that require detailed vision.

The acute form of AMD is “wet”. This results from the growth of new blood vessels at the back of the eye, and causes sudden loss of vision.

The more insidious “dry” AMD accounts for one-third of diagnosed cases and involves a slow, progressive loss of vision that is incurable. “Dry AMD kills the layer of cells in the back of our eyes – the retina,” says Dr Krisztina Valter of The Vision Centre and The Australian National University.

The damage caused by dry AMD was considered permanent until a discovery by the Centre’s scientists that key vision cells, when harmed, don’t truly die immediately but only become dormant. “The cones – vision cells that allow us to see in detail and colour – look unhealthy but they hang in,” Valter says “This means that there’s an opportunity for them to recover if we remove whatever’s stressing them.”

Vision Centre scientists have now developed several promising techniques to resurrect the inert cells and restore lost vision. These treatments are easy to use, painless and free of side-effects.

One of them is the use of gentle near infra-red light. The beneficial effect of near infra-red light was first discovered by astronauts in space, who found that cuts on their hands healed faster when they worked in near infra-red light.

Valter and her team have found that shining gentle red light with a wavelength of 670 nm into the eyes not only reduces the damage caused by over-exposure to bright lights, but also protects the eyes from subsequent harm.

“As the most energy-hungry cells in our body, vision cells rely heavily on the powerhouse of the cell – mitochondria,” Valter says. “While free radicals are produced in the process, healthy vision cells are usually able to fight them.”

However, when the vision cells are stressed, the process of energy production becomes unbalanced, leading to an overwhelming amount of free radicals. The now unhealthy vision cells are also unable to fight the free radicals, which proceed to damage all the cells in the retina.

Valter says that red light can help save the cells: “First, they increase the mitochondria’s ability to produce more energy, which boosts the cells’ ability to survive. The light encourages the mitochondria to also use oxygen more efficiently, leading to fewer free radicals. So you now have fewer damaging free radicals, and the cells also have enough energy to fight them.”

“Once the cells can repair themselves, they then regain their function,” explains Prof Jonathan Stone of the University of Sydney.

Another promising defender of sight comes in the form of the golden culinary herb, saffron, which is made from the heart of the crocus flower. Used in ancient Assyria, Greece and Rome to heal various ailments, science has shown that the herb is a powerful antioxidant.

Prof Silvia Bisti of The Vision Centre has carried out human trials using saffron to treat AMD with notable success. Bisti began studying the effects of saffron at L’Aquila, in Italy’s mountainous Abruzzi country, because it was a widely-grown local crop. It was already well-known as an antioxidant, but no one had explored its effects on eyesight before. “The point about saffron is that it is completely safe and harmless,” she says. “It has been used in cooking and medicine for 3000 years.”

In her trials, which were carefully controlled, patients with an early form of AMD had their vision partially restored by ingesting 20 mg of saffron every day for 3 months. “We don’t know what it is yet, but there’s something in saffron that interacts with our genes and stimulates the protection of nerve cells, including those in the retina,” Stone says. “Saffron also stabilised the retina against further degeneration for over a year for these patients. Being able to stabilise AMD and to restore vision – at least partially – are scientific dreams, and both now seem possible.”

The scientists are now working to understand the process and trying to make the temporary healing permanent.

Valter says that isolating the main cause in AMD is the real conundrum: “Some genes will put you at a higher risk of getting the disease, but there are other stressors, such as smoking, over-exposure to bright lights and poor diet, which also play a part in its development.”

The complexity of this devastating disease is affirmed by the Centre’s recent discovery of another culprit. “Up to a few years ago, some scientists thought that the key player in AMD was an immune system that had ‘gone wild’, but we didn’t understand why,” says Prof Jan Provis. “We knew that damaged cells invoke an immune response that calls in macrophages – white blood cells that ‘eat’ dead cells – to clean up the mess,” she says. In the case of AMD, the out-of-control response calls in more and more macrophages that eat away even more cells, including the healthy ones, so the damaged area gets bigger and bigger.

“But there’s something else apart from a malfunctioning immune response,” Provis says. “AMD is also caused by faulty micro-RNA molecules, which are unable to regulate the retina genes properly. This is a relatively new perspective on the development of dry AMD.”

Besides providing another target in the fight against the disease, her findings have thrown a new light on it. “It shows how complex these disorders are,” Provis says. “There’s no simple quick fix, so the challenge is to identify the best and most cost-effective way to intervene.”

While AMD is most commonly found in elderly people, Prof Christopher Nolan of the ANU says that diabetic retinopathy is the leading cause of blindness in working-age people who have Type 1 or Type 2 diabetes. Diabetes currently affects one in twelve Australians over the age of 25, and this is projected to rise. Of great concern is the increasing number of obese young people who already have Type 2 diabetes and retinopathy.

Nolan explains that the disease damages normal blood vessels in the retina: “In response, new vessels that grow are abnormal and can leak, bleed and cause sudden loss of vision”. Retinopathy also causes fluid to accumulate in the macula – the part of the eye responsible for detailed vision.

“The increasing prevalence of diabetes means that more people will need treatment and eye tests, which come at a high cost both to patients and to society,” Nolan says.

“Advanced stages of diabetic retinopathy require high intensity laser treatment to control the abnormal leaking blood vessels, which is expensive and laborious,” Nolan says. “The key is to prevent it from getting to the phase where ‘rescue therapy’ is needed, and accurate eye tests play a crucial part in this.”

Prof Ted Maddess’ team at The Vision Centre has developed an instrument named the TrueField Analyzer to provide simple, fast and accurate eye tests for serious eye diseases like AMD, glaucoma and diabetic retinopathy. The device requires the patient to look into the machine, and captures their pupil responses to test images on a screen using a video camera with infrared lights.

“An indication of a good pupil response is the speed and the size of its contraction – healthy eyes have bigger responses and react quicker,” Maddess says. By providing multiple stimuli at various locations in the person’s visual field, doctors can tell how well each part of the retina is functioning.

“Current tests for diabetic retinopathy include photographing the retina, using eye charts or asking patients to physically respond to a stimulus,” Nolan says. “However, these tests are often subjective and don’t provide enough detail. For instance, you need to have a pretty severe change in the retina before it’s visible in the photographs.”

A test on the speed and sensitivity of the pupils, on the other hand, measures the retinal function. This means that doctors and optometrists can quantify the amount of improvement – or deterioration – of the patient’s eyes. They can then tell whether a particular treatment is working, or if the patient is managing their disease well, possibly saving their sight.

An important breakthrough in restoring vision was the successful implantation of the world’s first bionic eye in a blind patient. In 2012, Australian scientists surgically inserted a prototype of the robotic eye in a woman who had retinitis pigmentosa, who later said that she could see spots of light. Scientists are working with her feedback to develop a processor that can build images using these flashes of light, and Prof Michael Ibbotson is testing components of the retinal prosthesis at the University of Melbourne.

While the researchers refine the techniques to defeat these sight-stealers and others including retinitis pigmentosa and Parkinson’s-damaged eye, Provis cautions that prevention of eye disease is also vital. As obesity contributes to both AMD and diabetes, she says: “It’s not just obesity that we have to deal with – it’s being obese and going blind at the same time.

“So exercise regularly to keep a normal blood pressure,” she says. “Eat your fish and plenty of leafy greens. Wear sunglasses. Don’t smoke. If you do all those things, your chances of avoiding severe vision loss as you age will be much improved.”

Mandy Thoo is a freelance science writer.