Some people claim that it is impossible to see the future of the ever-expanding field of biochemistry. However, with the retinal implants currently being developed, many more people will have the chance to see it. Straight out of Star Trek, bionic eyes are nearly here. Around 1988, it was first demonstrated that a blind person could be stimulated to see points of light by application of very small electrical currents to the nerve ganglia behind the eye. Ganglia are collections of neural cell bodies found throughout the body and are involved in carrying electrical impulses to the brain. This finding allowed several groups of scientists around the United States to believe it possible to create a microchip which would restore vision to at least some of the more than 10 million people suffering from retinal pigmentosa and age-related macular degeneration. To this point, science has been unable to create the partitions in the brain to allow sight. In other words, if early in development an individual does not develop the circuitry in their brain responsible for processing what he or she sees, science can not induce those pathways to grow. Subsequently, any person receiving an implant must have had normal development of the visual system early in life with later damage or degeneration of the cones and rods of the eye (see later). The optic nerve and the associated ganglia must also remain intact and functional for the current implants to work.
The Eye
The normal human eye is a complex device that transforms light of different wavelengths, and hence different colors, into electrical impulses. When received by the brain, these electrical impulses are translated into images by a mechanism that we do not yet understand. The primary components of the well-understood light conversion system include the rods and cones (the photoreceptors of the eye), the retina (the converter from light into electrical signals), and the optic nerves carrying the information from the retina to the brain. When light impinges on the eye, it is absorbed by photoreceptor cells of two kinds, rods and cones, named for their respective shapes. The rods are concentrated in the peripheral parts of the retina and function as "black and white" detectors. They are capable of responding to a single photon of light but are unable to decipher between different wavelengths and so provide the brain with only coarse black and white images along with a sense of movement and shape. The rod cells of the eye have two major components: light absorbing discs forming an outer segment and an inner segment rich in mitochondria and ribosomes. The cell membrane of a rod contains cation-specific channels that are open in the dark. These channels are specific for sodium ions that flow into the outer segment. These channels, together with the Na+-K+ ATPase pumps in the inner segment, maintain an electrochemical gradient across the membrane. Also in the membrane of the outer segment discs are found molecules of rhodopsin, the light sensing component of the rods. Rhodopsin is a seven-helix transmembrane protein that contains in its core a molecule of 11-cis-retinal. This retinal when exposed to a single photon of light is transformed into all-trans-retinal and undergoes a small conformational change. This change of shape initiates an enzymatic pathway leading to the closure of many of the cation-specific channels. The closed channels block the flow of more than a million sodium ions into the outer segment of the rod cell and cause a hyperpolarization of 1 millivolt. Hyperpolarization refers to the movement of charged molecules either into the cell, out of the cell, or both, resulting in a change away from the normal potential (charge difference) across the cell membrane. Finally, the change in electric potential across the membrane, albeit very small, is enough to stimulate the retinal cells to assemble and send an electrical message to the brain. As the retinal is transformed back to 11-cis-retinal, the cation-specific channels are returned to their normal open state allowing the inflow of positively charged sodium ions. The resting potential of the rod cell is restored. Calcium, as well as sodium flows in through these membrane channels. When these channels are closed by the rhodopsin reaction, the calcium concentration in the cell drops. This change leads to a different enzymatic pathway that restores the rod cell to the dark state so that it is ready to absorb another photon of light.
The cone cells in the eye are concentrated in the center of the retina and are found in much greater numbers than the rods. Their primary function is to allow differentiation between colors and to provide resolution to images. The cone cells require more than a single photon of light to be activated, accounting for the lack of color and resolution in night vision. Each cone cell contains one of three different receptors specific for wavelengths of light corresponding to blue, green or red color. These photoreceptors are proteins very similar to the rhodopsin found in the rods (see above). They are seven helix motif proteins containing a molecule of 11-cis-retinal. The three different photoreceptors are tuned to different maximum absorption wavelengths by the specific amino acid residues located near the retinal molecule. The exchange of a polar residue for a nonpolar residue at each of the positions near the retinal molecule will shift the maximum absorption towards the longer wavelengths by about 10 nm. The biochemical reactions governing the function of the cones are similar to those of the rods, primarily due to their similarity in structure. The cones send signals encoding color to the retina, which combines them with the signals from the rods and sends the resulting nerve (electrical) impulses via the optic nerve bundle to the brain. The brain then interprets the signals into shape, color, and depth. Since each cell contains only one receptor type, each cell sends a signal for only one color to the brain.
The search for a way to restore some degree of vision to individuals with degenerated retinal cells has been a long one. Given the extreme complexity of the eye as well as other issues like the acceptance of the microchip by eye tissue, the need for a constant power source, and the necessary resistance of the implanted microchip to the saline environment in the eye, it is no surprise that varying approaches are being taken in creating an artificial retina. One group, the Chow brothers of Optobionics Corporation, has pursued the creation of a silicon chip approximately 3 mm in diameter and 1/1000 of an inch thick. This chip is packed with thousands of microphotodiodes, each with its own stimulating electrode. Microphotodiodes are very small artificial receptors that absorb light similarly to retinal. The chip is inserted surgically into the subretinal space (see diagram) and functions as a replacement for the rods and cones of a normal eye. The Artificial Silicon Retina (ASR) is designed to convert the energy from light waves into electrical impulses which stimulate the optical nerve in much the same way as a functioning retina does. The ASR is powered by the light incident upon it, so it is not reliant upon any external battery for energy. In preclinical trials, animals implanted with the bionic retina responded to light and their optical nerves showed signs of electrical activity. Currently, Optobioinics Corporation is attempting to iron out bugs with the biocompatibility of the ASR as well as its durability in the saline environment of the subretinal space. Human clinical trials are slated to begin by the end of 2000.
A second group of scientists, working in a combined effort between NCSU and Johns Hopkins University, is developing an epiretinal version of the artificial retina. The silicon chip, developed by Dr Wentai Liu and associates at NCSU, is 2 millimeters square and coated with photosensor cells and electrodes. Differing from the ASR, the Artificial Retina Component Chip (ARCC) is powered by an external laser aimed at a photovoltaic cell implanted on the back of the eye. The laser is mounted on glasses that must be worn for the chip to function. The photosensors on the chip convert the light and images into nerve impulses, again, much like the normal human retina. This system is in essence a video camera which views an image, sends the information of the pattern of light in the image via the laser to the photovoltaic cell, which then stimulates the ganglia of the optical nerve to recreate a partial image. This image is really a rough pattern of light and dark areas that provides clues on the shape and size of whatever is being viewed. In this model, the electrodes do not pass current to stimulate the ganglia directly. Instead, the electrodes charge a plate that then stimulates the ganglia. This step is intended to reduce the risk of damage to the retinal tissue from the electrical current. This system is also scheduled for human testing to begin by 2001.
