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Wednesday, June 4, 2025

51��Ƶ researchers identify brain circuits responsible for visual acuity

Studies demonstrate the effect of retinal injury on visual processing pathways, providing insights for the development of vision restoration therapies.

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Visual processing involves interactions between neurons in the eye and brain allowing us to see the world around us. These pathways originate in the retina, which converts light energy into electrical signals that are transmitted to the brain's visual processing centers. Axons from retinal ganglion cells form the optic nerve, which connects to the lateral geniculate nucleus of the thalamus, a relay center in the brain that transmits signals to the visual cortex – a part of the brain that processes those signals into images.

Researchers at the National Institutes of Health (51��Ƶ) have identified which brain circuits are vital for visual acuity and how they are affected by damaged retinal cells. While vision restoration therapies, such as stem-cell and gene therapies, aim to replace or repair damaged cells in the eye, it is critical to understand how brain circuits involved in vision are affected by retinal cell loss. Study results suggest that targeting these circuits may be necessary to achieve optimal recovery of visual function, and have significant implications for the development of future vision restoration therapies that address visual pathways beyond the retina. The study published today in The Journal of Neuroscience.

“A huge amount of progress has been made in repairing the eye, however little attention has been paid to the functional consequences beyond the eye,” said the study’s lead investigator, Farran Briggs, Ph.D., senior investigator at 51��Ƶ’s National Eye Institute (NEI). “Brain circuits downstream of damaged or dying retinal cells in the eye may also undergo some loss of function following changes to their retinal inputs.”

Visual processing involves interactions between neurons in the eye and brain allowing us to see the world around us. These pathways originate in photoreceptor cells in the retina that convert light energy into electrical signals, which are then transmitted to the brain's visual processing centers. When retinal cells become damaged due to injury or disease, vision is often impaired. In a process known as neuroplasticity, the brain undergoes functional changes to adapt to a retinal injury or disease/degeneration. A person who experiences vision loss, for example, may have a resulting “blind spot” in a portion of their field of view.

Current therapies target retinal cells, however, retinal cells represent just the initial stage in a multi-step pathway that converts light into the complex images we perceive.

Scientists aimed to understand how neurons downstream of the retina are affected by damage to retinal ganglion cells (RGCs), which receive signals from other retinal cells and transfer to the brain. RGCs connect to neurons in a relay center in the brain, known as the lateral geniculate nucleus (LGN), that transmits signals to the visual cortex, where those signals are processed into images. The study examined two types of LGN cells that respond to different types of visual information and form parallel processing pathways: X-LGN neurons, which contribute to visual acuity, and Y-LGN neurons, which contribute to motion perception.

Investigators examined the effects of retinal cell loss on the X and Y visual processing pathways by using an animal model in ferrets. Following injury to the RGCs in the retina, recordings of LGN neuronal responses were conducted to evaluate the impact on X and Y pathways. They found that X-LGN neurons didn’t respond properly to visual stimuli, whereas Y-LGN neuron responses remained largely intact. These findings suggest that retinal cell loss affects downstream visual pathways differently, with the X pathway being notably impacted while the Y pathway remains relatively unaffected, suggesting higher sensitivity of visual acuity pathways to degeneration of the retina.

“Vision restoration therapies may need to target circuits that are responsible for visual acuity in addition to the retina. Such therapies could include training therapies, such as video games, that provide interactive feedback or other vision behavioral therapies,” Briggs said.

Future studies could use the model of RGC loss to investigate retinal degeneration and visual deficits in neuropsychiatric illnesses like schizophrenia. The research group aims to understand the marked changes in visual perception that occur during this disease.

This work was supported by the in-house research program at 51��Ƶ/NEI.

About the National Institutes of Health (51��Ƶ): 51��Ƶ, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. 51��Ƶ is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about 51��Ƶ and its programs, visit www.nih.gov.

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Reference

Yang, J., et al. (2025). "Differential impact of retinal lesions on visual responses of LGN X and Y cells." The Journal of Neuroscience: DOI: 10.1523/JNEUROSCI.0436-25. 2025.