Hereditary blindness caused by a progressive degeneration of the light-sensing cells in the eye, the photoreceptors, affects millions of people worldwide.
Although the light-sensing cells are lost, cells in deeper layers of the retina, which normally cannot sense light, remain intact. A promising new therapeutic approach based on a technology termed “optogenetics” is to introduce light-sensing proteins into these surviving retinal cells, turning them into “replacement photoreceptors” and thereby restoring vision. However, several factors limit the feasibility of a clinical optogenetic therapy using traditional light-sensitive proteins, as they require unnaturally high and potentially harmful light intensities and employ a foreign signaling mechanism within the target retinal cells.
New research publishing May 7th in the Open Access journal PLOS Biology from van Wyk and colleagues demonstrates how optogenetic proteins can be tailored to bring this promising technology closer to medical application. “We were asking the question, ‘Can we design light-activatable proteins that gate specific signaling pathways in specific cells?’, in other words, can the natural signaling pathways of the target cells be retained and just modified in a way to be turned on by light instead of a neurotransmitter released from a preceding neuron?” says Dr. Sonja Kleinlogel, corresponding author of the paper (whose research group is based at the University of Berne, Switzerland). The aim of molecular engineering was to achieve maximal compatibility with native signaling whilst retaining all the advantages of traditional optogenetic proteins, such as fast kinetics and resistance to bleaching by light.
The novel light-sensing protein, termed Opto-mGluR6, is a chimeric protein composed of the light-sensing domains of the retinal photopigment melanopsin and the ON-bipolar cell-specific metabotropic glutamate receptor mGluR6, which is naturally activated by glutamate released from the photoreceptors and amplifies the incoming signal through a coupled intracellular enzymatic pathway. Unlike rhodopsin, for example, the “light antenna” of melanopsin is resistant to bleaching. In other words, the response strength of Opto-mGluR6 never attenuates, no matter how often and hard the protein is hit by light. Moreover, since Opto-mGluR6 is a chimeric protein consisting of two “local” retinal proteins it is also likely to be “invisible” to the immune system, another improvement over traditional optogenetic proteins.
In their study van Wyk and colleagues targeted the retinal ON-bipolar cells, which naturally receive direct input from the photoreceptors. Targeting the surviving cells at the top end of the visual cascade has the advantage that signal computation of the retina is maximally utilized. Turning the native chemical receptor (mGluR6) into a light-activated receptor ensures conservation of native signaling within the ON-bipolar cells, conferring high light-sensitivity and fast “normal” responsiveness. In their study they show proof-of-principle that mice suffering from Retinitis pigmentosa can be treated to regain daylight vision. “The new therapy can potentially restore sight in patients suffering from any kind of photoreceptor degeneration” says Dr. Kleinlogel, “for example also those suffering from severe forms of age-related macular degeneration, a very common disease that affects to some degree about one in every 10 people over the age of 65”.
“The major improvement of the new approach is that patients will be able to see under normal daylight conditions without the need for light intensifiers or image converter goggles”
Read more: Light in sight: a step towards a potential therapy for acquired blindness
The Latest on: Optogenetics
[google_news title=”” keyword=”Optogenetics” num_posts=”10″ blurb_length=”0″ show_thumb=”left”]
via Google News
The Latest on: Optogenetics
- Study shows that astrocytes integrate information about past events in their somaon May 9, 2024 at 7:00 am
Neurons are known to communicate and integrate information they receive from their dendrites, branch-like structures extending from their body. In contrast, the activity in astrocytes, a class of star ...
- The Advent Of Tech In Science: How Optogenetics Seeks To Further The Development Of ‘Bionic Eye’on May 7, 2024 at 3:07 am
Once a topic of science fiction and lore, the idea of restoring eyesight is finally becoming an approachable reality. Today, the idea of building visual prosthesis has become less the subject of ...
- Demystifying Vision: Optical Illusions Illuminate Neural Pathwayson May 2, 2024 at 4:19 pm
Optical Illusion Helps Demystify the Way Vision Works For the first time, research shows that a certain kind of visual illusion, neon color spreading, works on mice. The study is also the first to com ...
- Beyond Human Perception: Study Unlocks Secrets Of Consciousnesson April 28, 2024 at 4:31 am
The study introduces the phenomenon of neon color spreading, an optical illusion observed in humans, and explores its effects on mice for the first time.
- Illusion demystifies the way vision works: Experiments imply brightness perception occurs deeper in brain than thoughton April 26, 2024 at 8:13 am
For the first time, research shows that a certain kind of visual illusion, neon color spreading, works on mice. The study is also the first to combine the use of two investigative techniques called ...
- Optogenetics News and Researchon April 23, 2024 at 5:00 pm
In a breakthrough for cancer research, scientists at EPFL have created lab-grown mini-colons that can accurately mimic the development of colorectal tumors, offering a powerful new tool for ...
- Restoring sight is possible now with optogeneticson April 23, 2024 at 3:30 am
Several companies are experimenting with optogenetics to create a “bionic eye” that can restore sight in visually impaired people.
- “Zombie neurons” shed light on the cerebellum's critical teaching signalson April 1, 2024 at 5:00 pm
In our experiment, we used a technique called optogenetics. This method functions like a highly precise remote control for brain cells, using light to turn on or off certain cells of interest at ...
- Optogenetics For 100 Euroson August 4, 2017 at 12:49 am
Larval zebrafish, Drosophila (fruit fly), and Caenorhabditis elegans (roundworm) have become key model organisms in modern neuroscience due to their low maintenance costs and easy sharing of ...
via Bing News