"Sunglasses" In The Eye

Researchers at the Max Planck Institute for Brain Research, Frankfurt/Germany in collaboration with researchers at the CNS Research group of the pharmaceutical company Novartis, Basel/Switzerland, detected a protein in the terminals of the photoreceptor cells of the eye that might play an important role in the transmission of the light signals (Proc. Natl. Acad. Sci. USA 96, 9909-9914; August 17, 1999).

The light energy caught by the eye is converted into neural messages and are transmitted to the higher visual centers in the brain where the images of our surrounding world come into existence. The light-perceiving, sensory part of the eye is the retina, which lines the back of the eye in a thin neural sheet.

The light-sensing retina is distinguished by its remarkable power to function over many orders of magnitude of light intensities. In sunlight the retina is bombarded by billions of photons, in darkness only few photons hit the retina. In spite of it, we are able to watch the moon and the stars in the night sky. No camera, no physical measuring device, can achieve such a degree of performance. In the following it is described how the retina might use a molecular feedback mechanism to adapt its working range to changing levels of light intensities.

Of key importance for the function of the retina is the conversion of photons into neural signals in the photoreceptor cells and the transmission of the signals to the postsynaptic neurons. For signal transfer the photoreceptor cells release a chemical messenger, glutamate, and the postsynaptic neurons possess receptors for the glutamate.

A mechanism that might play an important role in the first steps of signal transmission from the photoreceptor cells to the postsynaptic neurons has been recently discovered by the research group of Johann Helmut Brandstätter at the Max Planck Institute for Brain Research, Department of Neuroanatomy in Frankfurt/Germany. In collaboration with the research group of Rainer Kuhn (CNS Research, Novartis, Basel/Switzerland), the distribution and function of the metabotropic glutamate receptor 8, mGluR8, was studied in the retina. Employing immunoelectron microscopy, the Frankfurt group was able to detect for the first time a glutamate receptor in the terminals of the photoreceptor cells. Functional studies using isolated photoreceptor cells showed that the activation of mGluR8 triggers a chain of reactions leading to a decrease in the calcium concentration in the photoreceptor cells. The Frankfurt group concludes from this that the activation of mGluR8 leads to a downregulation of glutamate release from the photoreceptor cells, because calcium concentration and neurotransmitter release mechanisms are causally linked.

The concentration of glutamate at the synapse of the photoreceptor cells represents the light signal. A negative feedback mechanism, as shown for mGluR8, would downregulate the release of glutamate from the photoreceptor cells, and thus the activity of the postsynaptic neurons. This resetting of the working range of the synapse would lead to an expansion in the effective range of transmission of the light signals. This negative feedback inhibition prevents glutamate levels from reaching concentrations that would lead to the saturation of the postsynaptic glutamate receptors and thus loss of signaling capability or possibly even to the excitotoxic effects of glutamate. Or in other words: In our eyes we have a sort of Sun-glasses.