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Probing vision at the level of single photoreceptors

The eye with its transparent cornea and lens offers a unique view onto the neurosensory retina. Scientists at the Department of Ophthalmology at the University of Bonn are developing a microscope that makes individual human photoreceptors accessible for non-invasive experimental testing. This Emmy Noether project is funded by the German Research Council (DFG) with ~1.6 Mill. Euro.

Wolf Harmening is leading a DFG funded Emmy Noether Group at the Department of Ophthalmology in Bonn developing an innovative microscope to study single photoreceptor function.
Photo: UKB/Rolf Mülle

Studying the nervous tissue of the eye, the retina, in living subjects poses two main problems. First, the imperfect optics of the eye introduce higher-order aberrations that cannot be corrected with standard lenses, and thus limits any image forming process. Second, the eye is in constant motion, even when a subject attempts to steadily fixate. These fixational eye movements translate any point in object space over an array of photoreceptors in a non-systematic fashion, making controlled delivery of light intrinsically difficult.

Recent developments in ophthalmoscopic instrumentation now offer an effective way to overcome these problems, thereby offering the unique ability not only to image the retina with cellular resolution, but also to study photoreceptor function on single-cell level. A newly established DFG funded Emmy Noether Research Group lead by Dr. Wolf Harmening at the University of Bonn develops an adaptive optics scanning laser ophthalmoscope (AOSLO) to achieve that goal.

Figure 1: Adaptive optics (AO) allow visualization of individual photoreceptors in the live human retina.
Figure 2:
(Left): The AOSLO is a scanning laser instrument that can deliver light to individual photoreceptor cells by adaptive-optics corrected focusing of dedicated stimulation wavelengths.
(Right): A contiguous array of cone photoreceptors (N=138) was stimulated in a psychophysical experiment. Sensitivity thresholds are color coded and plotted at each tested location.

The AOSLO uses a deformable mirror to correct higher-order aberrations of the eye, such that light can be focused to extremely small spots on the retina. Fast image registration algorithms counteract eye motion in real time, granting a retina-contingent retinal display where single cells are stabilized in space and are easily selected for stimulation. High-frequency optical modulators are used as light switches to deploy dedicated stimulation wavelengths parallel to the imaging wavelength. Chromatic aberrations of the eye can be measured and corrected by a specific recording technique, bringing all wavelengths to the same focus at a targeted retinal location.

By combining these techniques in a single instrument, the researchers will be able to carry out functional testing at the cellular level in the retina. This will create new opportunities for vision and neuroscience and for the assessment of retinal disease in clinical studies. In the clinic, this new level of detail will help characterize retinal disease progression earlier and monitor pharmaceutical intervention at the level of individual photoreceptors in living subjects. This strategy may lessen the need of protracted histological validation in the development phase of novel treatments for retinal diseases. In addition to clinical applications, cell-level access to living neuronal tissue opens the door to study the basics of visual function with psychophysical methods at a previously inaccessible microscopic scale, to understand how visual perception is mediated by the activity of single neurons in the retina.

Wolf Harmening

Wolf Harmening (35) majored in Biology at the RWTH Aachen. He worked as a PostDoc in the Department of Zoology and Animal Physiology in Aachen to study visual perception in owls before he went to complete a second PostDoc at the School of Optometry in Berkeley on high-resolution retinal imaging techniques and visual perception in humans. He is now head of an Emmy Noether Research Group at the Department of Ophthalmology at the University of Bonn.

Contact

Wolf Harmening
Department of Ophthalmology
University of Bonn
Ernst-Abbe-Str. 2
53127 Bonn

Phone: 0049 228 287 15882
Fax: 0049 228 287 15603

E-mail: wolf.harmening[at]ukb.uni-bonn.de
Website: www.augenklinik.uni-bonn.de

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