Author: Ronja Jung (Germany)
Co-authors: Krunoslav Stingl, Carina Kelbsch, Melanie Kempf, Friederike Kortüm, Lisa Pohl, Katarina Stingl
Purpose
Studies on the electrical excitability of retinal neurons have shown that photoreceptors and other cell types can be selectively activated by distinct stimulation frequencies in vitro. The purpose of this project was to explore the possibility of cell-specific activation of retinal neurons in humans via transcorneal electrostimulation in vivo. Frequency-related differences in retinal responsiveness were evaluated objectively using the dynamics of the electrically evoked pupillary responses. Normal subjects were compared to patients with retinitis pigmentosa (RP) or achromatopsia to determine if the functional impairment of either rods or cones, respectively, would selectively manifest at specific frequencies.
Setting/Venue
1. University Eye Hospital, Center for Ophthalmology, University of Tuebingen, 72076 Tuebingen, Germany 2. Pupil Research Group, Center for Ophthalmology, University of Tuebingen, 72076 Tuebingen, Germany 3. Center for Rare Diseases, University of Tübingen, 72076 Tübingen, Germany
Methods
Eleven healthy participants, four achromatopsia patients (caused by mutations in the gene encoding the cyclic nucleotide-gated channel A/B3), and eleven RP patients (caused by mutations in either rhodopsin or phosphodiesterase 6A/B) were recruited to examine pupillary responses and phosphenes during transcorneal electrostimulation. The applied currents were composed of amplitude-modulated sinusoids, containing a low-frequency envelope that was superimposed on variable carrier frequencies (4-30 Hz). During stimulation of one eye, consensual pupillary oscillations were recorded from the contralateral eye via infrared pupillography. The responsiveness of the retina was assessed by the delay of the oscillations relative to the sinusoidal envelope and its variation throughout the measurement. The patients’ residual function of rods and cones was evaluated via chromatic pupil campimetry.
Results
RP patients had extinguished rod function but rather preserved cone function. Vice versa, achromatopsia patients had normal or enhanced rod activity but mostly no measurable cone function. Electrically-evoked pupillary oscillations following the sinusoidal envelope could be observed in all three groups. The calculated responsiveness of the healthy retina displayed a distinctive peak at 6-8 Hz. This peak was strongly enhanced in achromats but completely absent in RP patients. Correspondingly, achromats had strong phosphenes in the low frequency range, while RP patients reported to have only faint light perception. Healthy participants then showed sudden reduction in responsiveness in the middle frequency spectrum, followed by a second gradual increase at higher frequencies up to a local maximum around 24-26 Hz. Though relatively weaker, RP patients displayed a similar increase with higher frequencies. Achromatopsia patients, however, had poor responses throughout the entire upper frequency range, which was usually accompanied by a lack of phosphene percepts.
Conlusions
The observed differences in the pupillary responses and phosphenes between healthy subjects and patients with impaired rod or cone vision suggest that responses around 6-8 Hz are mainly mediated by rods, while cones seem to be responsible for the increase in responsiveness in the upper frequency range. In sum, this work provides more evidence that different retinal cell types can be selectively activated with specific frequencies. To investigate the frequency preferences of inner retinal neurons, appropriate disease models will be investigated.
Financial Disclosure
none
Comments
-
