The retina is often called an “outpost of the brain” because crucial visual signal processing happens in the eye’s nerve cells rather than in the cerebrum. When light strikes the retina, specialized sensor cells activate and transmit electrical signals to the nerve cell layers directly behind them. These signals are then conveyed to the brain, enabling vision. Nonetheless, the precise manner in which the retina’s signals are processed by the nerve cells was previously unknown.
A recent research conducted at TU Wien (Vienna) has now revealed that the retinal ganglion cells, which are the nerve cells of the retina, can adopt varying roles and thus perform distinct functions related to vision. Remarkably, they maintain this capability even when portions of the retina undergo degeneration, which is promising for the potential restoration of vision in individuals who are blind, particularly through the use of electronic retinal implants.
“When light falls onto the photoreceptors of the retina, electrical signals are generated in the nerve cells behind them,” says Paul Werginz from the Institute of Biomedical Electronics at TU Wien. “But not all nerve cells produce the same sequence of signals.”
When the light is turned on or off, specific types of nerve cells consistently activate. Yet, in certain cells, the signal frequency rapidly diminishes, whereas other cells maintain a relatively high activity level and persist in generating a strong electrical signal. The reasons behind these varying activity patterns have not been understood. After all, one would anticipate that cells of the same type would respond in a similar manner.
“The question for us was: if the retinal ganglion cells behave differently, is it because they are integrated into different biological circuits and, therefore, receive different input signals? Or is there an intrinsic difference based on biophysical principles that causes these cells to produce different signals, even if they receive identical inputs?” says Paul Werginz. “In the second case, each ganglion cell type could be assigned its own component ID, so to speak.”
To investigate this, the researchers utilized retinas that had been extracted from mice, maintaining the full functionality of the neuronal network for several hours. The retinal ganglion cells can be stimulated in two distinct manners: by shining light on the retina and analyzing how the ganglion cells respond, or by directly applying electric current to stimulate the ganglion cells.
Through the direct application of electric current, it becomes possible to examine the neurons’ characteristics without the influence of the cells that normally send them signals.
“We found that when we directly stimulate the cells with electric current, they show a signaling pattern very similar to the one they produce when exposed to light,” says Paul Werginz. “Ganglion cells that show an increased activity pattern for a longer time period when exposed to light also do so when electrically stimulated.”
This suggests that the variation in signaling patterns among these cells is not solely attributed to differences in the inputs they receive within the retinal circuitry – rather, the inclination to generate longer or shorter signaling sequences is an inherent characteristic of the cells themselves.
“This is astonishing but is likely to be very important for signal processing and vision,” believes Paul Werginz. “These differences between the cell types probably arise very early on, during the developmental phase of the retina.”
The question is if these cells possess intrinsic properties, do these features remain consistent even when the cells lose their original function, such as when the retina’s photosensors cease to operate? One might expect that the behavior of these cells would alter in such circumstances. After all, it is well-documented that unneeded nerve cells undergo reorganization within the brain.
In contrast, retinal ganglion cells exhibit a different resilience: “We examined the cells of mice that had been blind for 200 days, and their retinal ganglion cells still showed exactly the same properties: some could be made to be active for a short time with electrical input, others for longer,” says Paul Werginz.
The cells therefore retain their inherent capability to transmit specific signals. This is promising news for the advancement of retinal implants that utilize electrical stimulation through thousands of electrodes to compensate for the lost photoreceptors in individuals with blindness, according to Paul Werginz.
“If there are stable differences between different cell types, then the existing ganglion cells can be utilized even after blindness, and better stimulation strategies can be developed for them in the future,” he said.
Journal reference:
- P. Werginz, V. Király and G. Zeck. Differential intrinsic firing properties in sustained and transient mouse alpha RGCs match their light response characteristics and persist during retinal degeneration. Journal of Neuroscience, 2024; DOI: 10.1523/JNEUROSCI.1592-24.2024