Blindness has several causes. Cataract is treated surgically and glaucoma with eye drops or surgery. Other causes are trauma, abnormal blood vessel growth in premature birth and diabetes, macular degeneration, and genetic conditions, especially retinitis pigmentosa. In developing countries blindness is also caused by vitamin A deficiency and two infectious diseases, trachoma and onchocerciasis (river blindness).
Research in a strain of blind mice has highlighted the importance of a DNA-degrading enzyme that helps the developing lens in the eye to remain transparent. The lens is made up of clear fibre cells. As they form, their internal structures, such as the nucleus and power-boosting mitochondria, are broken down to prevent the lens from becoming cloudy. Mice lacking an enzyme called DLAD were unable to degrade fibre cell DNA, and they developed cataracts. DLAD is also found in human lens cells, so some cataract patients probably have a deficiency in the DLAD gene.
Glaucoma is the most important cause of irreversible blindness worldwide, affecting more than half a million people in the UK alone. It is caused by increased fluid pressure within the eye compressing the nerves at the back of the eye. This pressure then causes irreversible damage to the optic nerve at the back of the eye. Patients require surgery to create a new channel in the eye to drain away the excess fluid and reduce the pressure. However, the channel can become blocked because of scarring and this leads to the failure of the operation, and blindness. The potential success rate of glaucoma surgery was been greatly improved – rising from 30% to an impressive 80% in rabbits – by innovative and safe new drugs that can prevent scarring in the eye after glaucoma surgery. This success has encouraged researchers to plan clinical trials in humans.
The blindness of diabetes and prematurity is caused by abnormal blood vessel growth. In mice an eye protein, pigment epithelium-derived factor, has halted this
Retinopathy of prematurity has become a leading cause of defective vision in children because medical advances enable more premature babies to survive. Half the babies with the severest form of the disease will become blind despite treatment. They are missing an enzyme called beta-galactosidase, made by the ß-gal gene. Research has shown that a harmless adenovirus can transport the gene into the defective eyes of baby rats. The gene specifically targeted the correct tissues inside the eyeball, avoiding delicate adjacent nerve cells, and may therefore be the first step towards gene therapy .
Scientists have identified a protein in mice called HIF-2a, which is important in retina formation. Controlling this protein, which is also found in humans, may help treat or even prevent retinopathy of prematurity .
Diabetic retinopathy is the leading cause of blindness in people aged 20–74. Research on rats shows that a common antibiotic called minocycline, used to treat acne, halves the retinal damage caused by microglia. These are cells that act as the 'cleanup crew' for the central nervous system and retina. They destroy damaged cells by releasing toxins and they engulf them. When they become activated and release their toxins in the retina, those toxins will kill the healthy nerve cells critical for normal vision .
Retina cells are a type of nerve cell, and do not normally recover when damaged. Scientists have now found that, in mice, certain cells from the retinal margin function as stem cells. In culture, these cells will multiply and develop into typical retinal nerve cells. Tremendous potential exists if this developmental flexibility can be manipulated for human benefit.
In rats with retinal disease, researchers found that nerve stem cells injected into the eye migrate to the retina and appear to take on the right characteristics. Even more exciting, they also show signs of trying to connect the retina to the brain, an essential step in restoring sight. Neurologists subsequently found a way to reconnect severed optic nerves to the brain so that they once again transmitted normal electrical signals. The achievement is a first in mammals, and may lead to human treatments
A bionic eye implant – a 3mm chip that would fit behind the retina – could be a dramatic improvement on currently available technology. In a rat study, researchers showed that by placing the chip behind the retina, the remaining living retinal cells moved closer to the photodiodes on the implant. The closer the cells get to the array, the better the resolution of the image. The goal is no more than 10 microns between the retinal cells and the implant, equivalent to the width of one cell. When the implants were used in blind rats, the rodents appeared to have some restored vision, responding to a pattern of black and white stripes. A visual acuity of 20/20 is considered normal, while 20/400 is considered blind. The device could provide acuity of 20/80, good enough to live independently and read large print .
The most sensitive part of the retina is the macula. Age-related macular degeneration affects 180,000 elderly people in the UK, and Stargardt blindness is a rare variant affecting young people. The only treatment is expensive and inadequate. Patients lose central vision and hence the ability to read, but can usually recognise objects on the edge of the visual field ('out of the corner of their eye'). A similar condition occurs in young rats. In 2002 a team of eye surgeons and scientists removed cells from the retina, took them back to a primitive condition that made them unlikely to be rejected, grew them in a test tube, and injected them into rats. The rats, which had been given both human and rat retina cells, retained the cells and didn't go blind. Human trials are planned in 2003 .
The underlying mechanism of macular degeneration is blood leakage from stray blood vessels below the retina, called choroidal neovascularisation. A new cancer drug, combretastatin (CA4P), has been found to prevent and treat this in mice, and human trials are planned .
Researchers have also found a potential way to replace damaged rod and cone cells in the retina, using rats. The genetic technique, in which iris cells are modified in the laboratory and transplanted back into the retina, could some day prevent blindness from macular degeneration and retinitis pigmentosa .
Retinitis pigmentosa is an inherited condition initially causing night blindness and progressing relentlessly. The gene Prph2 is defective in human RP, and mice that lack it have damaged photoreceptor cells in the retina. These photoreceptors regained their normal structure and responded to light when the missing gene was introduced, suggesting that the mice were able to see. This successful introduction of the missing gene into the eyes of mice may eventually lead to human gene therapy .
In 2002 researchers discovered two mutations in dogs that promise to contribute greatly to studying causes and testing treatments for inherited blindness in pet dogs and humans. Many Siberian huskies and Samoyeds carry the genes XLPRA1 and XLPRA2 cause X-linked progressive retinal atrophy, the canine equivalent of retinitis pigmentosa . In 2005 scientists discovered that retinal injury can be caused by moderate light exposure in dogs with RP. They therefore strongly recommend patients to limit excess light exposure .
Genetically engineered mice with retinitis pigmentosa promised to speed the search for a cure. In 2004 researchers injected newborn RP mice, which had yet to develop the condition, with blood stem cells taken from bone marrow. The injections appeared to halt some of the eye's deterioration, particularly that of the cone cells, which are responsible for colour and fine vision .
Leber congenital amaurosis is a rare genetic disease that causes near-total blindness during infancy, and a similar disease occurs in dogs. In 2001 scientists used gene therapy to restore the sight of a blind dog. Afterwards, sight tests indicated that the treated eyes were as good as the eyes of normal dogs. As revealed on video, the dogs avoided bumping into obstacles placed on the same side as the treated eye. This study provides hope that correction of human LCA is feasible .
In 2004 scientists studying mice showed that absence of the Aip11 gene causes loss of light-sensitive rod and cone cells, mimicking the inherited human disease. This gives scientists another model that can be used for testing potential treatments. They are now working to determine if they can prevent this disease by supplying the retinas of affected newborn mice with the missing gene .
In 2001 researchers got severed nerves to regrow up to 14 mm, more than three times as far as anyone has managed before. They severed the optic nerves of rats and sewed them together again under anaesthetic, and then added proteins called crystallins, which inhibit the mechanism by which cells self-destruct. Three months after the surgery, a third of the nerve fibres had regenerated. One tenth is sufficient for residual sight. The regenerated nerves also carried normal electrical signals, suggesting that they had rewired themselves into the brain, although the connections were scrambled.
Onchocerca is a parasitic worm that harms 6.5m people in Africa and South America, blinding many of them. Millions of infected patients are normally given the drug ivermectin, which targets the worms, which are now developing resistance to this drug. However, the real cause might be the Wolbachia bacteria that live on the worm, and which are susceptible to an inexpensive antibiotic. Mice infected with extracts from antibiotic-treated worms showed significantly less thickening and haze of the eye's cornea, and fewer overall signs of inflammation.
Retinoblastoma an eye cancer of children, the third most common cancer of childhood after leukaemia and nerve cancer. The five-year survival rate is less than 10%. Scientists working with mice have discovered that a tumour-suppressor protein called Rb1, made by a gene also called Rb1 is essential to the normal development of the eye, and children missing the gene are at high risk of developing retinoblastoma. The gene enables formation of light-receiving cells called rods, and prevents overproliferation of retinal cells. Further study promises to increase our understanding of the disease process and thus lead the way to a cure
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Last edited: 27 August 2014 06:07