Scientists unveiled the first steps in the construction of vision

By decoding the genetic mechanisms that control the neurons of the visual system, researchers at UNIGE are unveiling the first steps in the construction of vision, paving the way for regenerative eye medicine.

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Retinal ganglion cells (RGCs), cone photoreceptors (cones), horizontal cells and amacrine cells are the first classes of neurons created in the retina. Be that as it may, an important question is how this diversity of cell states is transcriptionally created.

The visual system of mammals is made out of various kinds of neurons, each of which must discover its place in the brain to empower it to enable it to transform stimuli by the eye into images. There are photoreceptors, which identify light, optic nerve neurons, which send data to the brain, cortical neurons, which form images, or interneurons, which make associations between different cells. In spite of the fact that not yet differentiated in the beginning periods of embryonic improvement, these neurons are altogether created by progenitor cells that, are fit for offering ascend to various classes of specific neurons.

To better understand the exact course of this mechanism and identify the genes at work during retinal construction, scientists at the University of Geneva (UNIGE), Switzerland, in collaboration with the École Polytechnique Fédérale de Lausanne (EPFL), have identified the genetic programmes governing the birth of different types of retinal cells and their capacity to wire to the correct part of the brain, where they transmit visual information.

Quentin Lo Giudice, PhD student in the Department of Basic Neurosciences at the UNIGE Faculty of Medicine and first author of this article said, “To monitor gene activity in cells and understand the early specification of retinal neurons, we sequenced more than 6,000 cells during retinal development and conducted large-scale bioinformatic analyses.”

Scientists studied progenitor’s behaviour during the cell cycle as well as during their progressive differentiation. They then precisely mapped the different cell types of the developing retina and the genetic changes that occur during the early stages of this process.

Pierre Fabre, senior researcher in the Department of Basic Neurosciences at the UNIGE Faculty of Medicine said, “Beyond their “age”—that is, when they were generated during their embryonic life—the diversity of neurons stems from their position in the retina, which predestines them for a specific target in the brain. In addition, by predicting the sequential activation of neural genes, we were able to reconstruct several differentiation programs, similar to lineage trees, showing us how the progenitors progress to one cell type or another after their last division.”

Scientists also conducted a second analysis. If the right eye mainly connects essentially to the left side of the brain, and vice versa, a small fraction of neurons in the right eye make connections in the right side of the brain.

Indeed, all species with two eyes with overlapping visual fields, such as mammals, must be able to mix information from both eyes in the same part of the brain. This convergence makes it possible to see binocularly and perceive depths or distances.

Quentin Lo Giudice said, “Knowing this phenomenon, we have genetically and individually “tagged” the cells in order to follow each of them as they progress to their final place in the visual system.

Scientists then compare the genetic diversity of these two neural populations and found 24 genes that could play a key role in three-dimensional vision.

Fabre said, “The identification of these gene expression patterns may represent a new molecular code orchestrating retinal wiring to the brain.”

Scientists thus identified the molecules that guide neurons on the right path as the the neurons must leave the retina through the optic nerve, before reaching to the brain. These same molecules are responsible for the initial growth of axons, the part of neurons that transmits electrical signals to the synapses and thus ensures the passage of information from one neuron to another, as well as about twenty genes that control this process.

Dr. Fabre explained, “The more we know about the molecules needed to appropriately guide axons, the more likely we are to develop a therapy to treat nerves trauma. If the optic nerve is cut or damaged, for example by glaucoma, we could imagine reactivating those genes that are usually only active during the embryonic development phase. By stimulating axon growth, we could allow neurons to stay connected and survive.”

“Although the regeneration capacities of neurons are very low, they do exist and techniques to encourage their development must be found. Genetic stimulation of the damaged spinal cord after an accident is based on the same idea and is beginning to show its first successes.”

These results can be discovered in the journal Development.

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