Photoreceptor Damage:

Causes and Possibilities

by John Angell

Over 10,000,000 people around the world suffer from some sort of blindness or handicap due to photoreceptor damage. These effects can be caused by a number of afflictions, including retinitis pigmentosa, macular degeneration, and tumors. These illnesses vary in severity from being a mere hindrance to completely blinding the individual. Until recently, those affected were left without hope of a cure or even a treatment that would somewhat improve their vision. But over the last few years, several groups of scientists have been working on a partial cure in the form of neuroprostheses, artificial devices which are inserted in the eye behind or on top of the damaged retinal area. These photoreceptive chips, in theory, should provide information too the healthy neurons residing in the retina, substituting for the damaged photoreceptors.

When we open our eyes, millions of tiny events occur that allow us to see. Our pupils automatically constrict in accordance to the light level, the variable lens bends and adjusts to fit the distance of what we are looking, and our photoreceptors receive information in accordance to the previous factors. (This is extremely simplified, but it will suffice for now.) Photoreceptors are tiny, specialized neurons located in the retina at the back of the eye. There are two types of photoreceptors, rods and cones. Each follow the same principles: when light hits them they respond with a chemical reaction using a substance known as rhodopsin. Once this reaction occurs a chain of events sends this message down a number of sophisticated and specialized neurons, eventually reaching the brain and resulting in what we call sight.

Rods (numbering one hundred million or so in each eye) are primarily in the periphery of our visual field. They are extremely sensitive to light and are often ÒtiedÓ together on a lower level to allow for greater sensitivity. Rods do not see in with good resolution and cannot differentiate colors.

Cones (only five million or so exist) are mostly found on the center of the visual field, a place called the fovea. The words you are reading now are being processed by cones in the fovea. They operate in brighter light than rods and detect color (there are three types, each responding to a particular range of wavelengths). Cones do not pool their output and exist for resolution, not mere detection. The only drawback with the cone system is the amount of light saturation necessary to stimulate them and send their signal to the brain. Cones require bright light and do not function in dim light, which explains why we only see in black and white while in the dark.

Working together, rods and cones create our visual field, resulting in astounding resolution and sensitivity when compared to most other animals. Unfortunately, nothing in nature is either perfect or infallible. Many different factors may affect and permanently damage these photoreceptors.

Perhaps the most common cause of photoreceptor failure is retinitis pigmentosa, which affects over 100,000 people in the United States alone. Very little is know about the cause of the disease, but a problem in the pigment epithelium, a layer of blood and nutrient supplying vessels beneath the photoreceptors, has been theorized. Retinitis pigmentosa begins in early adulthood, around the age of twenty, first damaging the rods on the periphery of the visual field, causing night tunnel vision.As the individual ages and the disease progresses, the visual field gradually decreases until the disease attacks the cones in the fovea, leaving many subjects completely blind. Retinitis pigmentosa is genetically inherited, but does not affect everyone with the retinitis gene.

Second on the list of crippling conditions which causes receptor damage is macular degeneration, the most common form known as age-related macular degeneration. The macula is an area of tissue measuring roughly 5mm in diameter surrounding and including the fovea. In early macular degeneration, the disease causes the cone receptors to thin slightly and small yellow lumps begin to form on the retina. This progresses slowly and may not cause any real problems at all. In up to 20 percent of the cases, however, the macula also experiences the formation of small new blood vessels (strikingly similar to diabetic retinopathy) which eventually break and bleed fluid into the vitreous humor (the jelly-like substance inside the eye). It only takes a few months for this leakage to destroy the cones. Macular degeneration is fairly common in older people and there has been some success in slowing its crippling effects using a laser to photocoagulate these new blood vessels and reduce their leakage. The perceptual effects of macular degeneration are the opposite of retinitis pigmentosa: peripheral and night vision remain remarkably intact but central and color vision are completely destroyed. In other words, the victim can see everything around what he or her is looking at but cannot see straight ahead at all. People suffering from this cannot read, drive a car, or even walk normally. Also they cannot see properly in bright light because the hypersensitive rods become oversaturated.

Diabetic retinopathy is a result of the invention on insulin. Until insulin was introduced, a diabetic could not expect to reach 25. But with the prolonging of life due to this miracle of medicine, new problems emerge. In the United States alone, over 4 million people suffer from diabetic retinopathy. In early stages, the capillaries in the retina begin to swell, squeezing the photoreceptors and causing visual impairment. Sometimes the disease stops here and only slightly hinders the sight of the victim. Other times, however, the disease progresses into what is known as neovascularization. As in macular degeneration, new and abnormally shaped blood cells form but actually cut off vital nutrients and oxygen to the retinal neurons, literally starving them to death. Neovascularization can also cause retinal scarring and detachment.

Less common forms of photoreceptor damage include optic neuropathy, vascular disturbance, tumors, extreme light damage. Tumors may slowly grow beneath the retina squeeze the photoreceptors until they eventually die. This results in patchy vision in whatever area is affected. Extreme light intensity is not common and is easily avoidable. Galileo suffered from damage to his photoreceptors when he trained his telescope on the sun in attempt to view its surface. Also, residents of Nagasaki and Hiroshima were blinded when they saw the flash of the first atomic bombs. The photoreceptors in their eyes were, quite simple, burned out.

As stated before, over 10,000,000 people worldwide suffer from damage to the retina and/or photoreceptors. That number can only be expected to grow in the future. Over the last few years, however, new possibilities have become available (though they seen extremely science fiction). Retinal implants, or neuroprostheses, which are wafer sized chips measuring only 3mm in diameter and 50 microns thick, have given hope to millions of people. They are similar in theory to the first sensory organ replacement, the Cochlea Implant, which dramatically improves the hearing to those suffering from certain ear conditions. Surgery for retinal implants is more invasive and more dangerous than the Cochleal Implant, but it is certain that many people are willing to take the risk.

The first of these neuroprostheses is being studied by a group of distinguished German scientists led by Professor Ebert Zrenner. The subretinal implant, or subret, is a tiny disk implanted within the damaged photoreceptors at the back of the eye. Once implanted, tiny microelectrodes connect to horizontal and bipolar cells which would normally be connected to the photoreceptors. On this disk are 7000 microphotodiodes arranged in a checkerboard pattern, each measuring only 20X20 mm (about the size of the photoreceptors in the retinal periphery). These microphotodiodes are composed of silicium oxide, which when struck by light release a positively polarized charge. This charge travels down the implant into a series of microelectrodes, which like the original photoreceptors stimulate the horizontal and bipolar receptors, resulting in sight. As of September 15, 1997, several rabbits have been given the subret implant and are currently under observation at the University Eye Hospital in Tubingen, Germany. Functional tests are being undertaken, and early results have been favorable. Also, the implants show remarkable acceptance to the rabbitsÕ ocular tissue. More in depth results have not been made public yet.

The second form of neuroprostheses is the epiretinal implant, or epiret. A team of American scientists led by Dr. Wentai Liu use a very different approach. The epiret is implanted inside the eye between the ganglia cells and is exposed to the vitreous humor. It is more alike the Cochleal Implant in that it must be powered by an external source. The epiret connects through the ganglia and amecrine cells into the horizontal and bipolar cells through the use of microelectrodes, resulting in similar results as the subret. One possible means of powering this device is the use of Òlaser glassesÓ. These special eyeglasses have a tiny laser mounted on them which, when activated, direct a beam into the eye and onto a special photovoltaic cell, which in turn powers the chip. Results from experiments using the epiret have been difficult to attain, but again the concept is quite promising.

Neuroprostheses provide hope to where there was none, but they do have limitations. The microphotodiodes on the surface of the implant are extremely large when compared to the natural cones in the fovea, and resulting vision will be blurry at best. Also, these diodes are not equipped to detect different wavelengths, so the subject would see only in black and white. But with the advancement of nanotechnology, these microphotodiodes will eventually become smaller and more complex. Another problem with the implant is the possibility of circulation being cut off to healthy retinal neurons, but a new approach using chain mail ordered structuring would open tiny ÒgatesÓ in the chips, just large enough for nutrients and oxygen to pass through.

Perhaps the biggest problem facing both groups of scientists does not lie in technology or availability of test subjects, but funding. In the United States, the neuroprosthesis operation is classified as Òhigh riskÓ, so no money from the U.S. government will sponsor them. German scientists are enjoying a 18 million Deutch Mark grant from the BMBF (the Federal Ministry of Education, Science, Research, and Technology). This generous donation is not enough, however, to fund the enormous research and development programs necessary to make advancements in this technology a reality. These problems, however, are minuscule when compared to the possible of restoring sight to those millions afflicted with photoreceptor damage.

Looking into the future, with proper funding, scientists will figure out how to make these microphotodiodes sensitive to certain wavelengths, allowing for color vision, and also make them smaller, increasing resolution. Compare this technology to that of microcomputers over the last ten years: in 1988 the fastest home computer measured around 8 megahertz; in 1998, computers have exceeded 300 megahertz. More on the edge of science fiction is the possibility of wavelengths normally invisible to average human eyes becoming detectable to those with retinal implants (humans being sensitive to infrared or ultraviolet light). The possibilities are limitless, provided funding is available.

References

8/18/97. Sub Retinal Implant Project. On-line: Web Page for Subret Project
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Johnson, Steven S. (1997). Solar cells may sub for retinal receptors. Science News, v151. 222-224.

Ready, Tinker (1997). A vision to bring back sight. The News and Observer. Online: Web Pabe for News and Observer .

Tovee, M.J. (1996). An introduction to the visual system. Cambridge University Press: New York, NY.

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