Mechanisms of myopia
How the retina can regulate the growth of the eyeIt has taken humans thousands of years to master the technology of making optics such as telescopes and cameras that produce good images. Yet on the surface of it, nature seems to have little difficulty producing remarkably precise optical surfaces and alignments within the eyes of most animals. How does nature manage to get the length of the eyeball right to within optical tolerances? This is a question that lies at the core of the research of Siobhan McCarthy from the Research School of Biological Sciences. Siobhan has just submitted her Doctoral thesis on the role of the retina in controlling myopia (short sightedness) and is about to begin a postdoctoral fellowship in the same area.
Siobhan explains that in most animals at birth, the eye is hyperopic or long-sighted. Structurally this means that the eye is shorter than ideal. In terms of practical vision, this isn’t a major problem because the animal can clearly see images at long distances and accommodate to see close objects clearly. As the animal matures the eye will grow and gradually the point of focus will become exactly correct. However in some people the eye becomes too long and thus myopic. This growth of the eye is thought to be at least in part, controlled by the neurotransmitter dopamine. Dopamine is released from specialized cells within the retina called dopaminergic amacrine cells. Dopamine release increases in response light and particularly flickering light which increases the temporal contrast in the image on the retina. In other words, the focused patterns of light and dark on the retina that occur during the process of normal seeing, actually stimulate the retina to produce chemicals which regulate the growth of the eye. By the use of this ingenious feedback mechanism, nature is able to manufacture a precision optical instrument using soft “goey” materials that would be a nightmare to a human engineer.
A large part of the motivation behind this work is to try to understand how the mechanism works so that we can develop better treatments for the cases when doesn’t. Myopia is becoming a large problem in many areas of the world, with some east Asian countries recording myopia rates as high as 90%. Whilst mild myopia can be treated with corrective lenses or even advanced laser procedures such as LASIK, extreme cases can lead to other serious complications. If the eye becomes extremely extended and highly myopic, this can lead to structural problems such as tears and detachments of the retina that are far more difficult to treat. There have been quite a few animal studies in which the influence of externally introduced dopamine agonists (mimickers) and antagonists (inhibitors) have been used to investigate eye’s development. Whilst such studies are valuable, Siobhan wanted to develop a different technique that was less invasive and that perturbed the natural mechanisms of eye development as little as possible. Her study was based on chickens that were fitted with little goggles. Over one eye a plastic diffuser allowed light through but frosted out any clear image, the other eye was left uncovered as a control. The chickens were then free to wander around their enclosure doing the normal things that chickens do. Over the course of their development, Siobhan measured the levels of dopamine and correlated this with the growth of both the covered and the control eyes.
Of course you can’t get a chicken to read an eye chart, so alternative measures of visual acuity must be employed. Because a myopic eye is a longer than a normal eye, Siobhan measured the length of the eye using an ultrasound scan of the eye which gives the spatial dimensions.
The research to date has supported the role of retinal dopamine in the control of eye growth but it has also highlighted some other surprising findings. In order to correctly regulate eye growth the retina does not absolutely need to have a contrasty image all of the time. Removing the diffuser for as little as three hours a day is enough to fully restore the regulatory growth mechanism. Siobhan also explored the rather surprising phenomena of intensity related dopamine stimulation. It appears that exposure to bright light can stimulate dopamine production even in the absence of any spatial contrast. She believes this may relate to the long standing observation that children in cities that spend a great deal of time indoors, tend to have higher rates of Myopia than those living in more rural areas that spend more time outside in brighter light.
The ultimate picture that emerges from this work is of a highly complex series of mechanisms by which the retina controls the development of the eye using dopamine and other chemical messengers. There is still a great deal to learn but the researchers hope that one day we may be able to create simple non-invasive treatments for children diagnosed with the potential for myopia. Such treatments may be able to restore the eyes defective regulatory mechanism and enable it to halt growth at the correct point. Siobhan acknowledges that it’s unlikely that any treatment can eliminate all visual defects in developing eyes, but even if it were possible to limit the severity of myopia in most patients, that would be a very worthwhile result.