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New Penn Study Finds Promising Model for Restoring Cone Function

02/12/2024
New Penn Study Finds Promising Model for Restoring Cone Function image

Vision scientists from the Division of Experimental Retinal Therapies at the University of Pennsylvania School of Veterinary Medicine used functional magnetic resonance imaging (fMRI) to assess brain responses to lights that stimulate only cone cells in dogs with naturally occurring retinal disease and with normal vision.

The researchers found that fMRI can detect brain responses to daylight vision for black and white information as well as color information, and it can identify the area of the visual cortex that responds to stimulation of a region in the dog retina that is rich in cones and similar to the human fovea, according to an article posted on the Penn Medicine website. The researchers also found they can use fMRI to measure the relative degree of loss of daylight vision. Using this technique in animals with a retinal disease caused by a mutation in a gene called NPHP5, they demonstrated that gene augmentation therapy restored the response in the cortex to black and white stimulation. That makes this disease a promising one in which to study photoreceptor cell replacement as a treatment in the future.

Their findings were published in Translational Vision Science & Technology. The other co-authors are Huseyin O. Taskin, a former research specialist at Penn in the GKAguirre Lab and current graduate student at the University of Toronto, and Jacqueline Wivel, a veterinary technician. 

In the retinas of human eyes, the cones are photoreceptor cells responsible for color vision, daylight vision, and the perception of small details. As vision scientists from the Division of Experimental Retinal Therapies at the University of Pennsylvania School of Veterinary MedicineGustavo D. Aguirre and William A. Beltran have been working for decades to identify the basis of inherited retinal diseases. They previously showed they could recover missing cone function by reintroducing a copy of the normal gene in photoreceptor cells.

Both humans and dogs are affected by retinal disease, and a new study of daylight vision using a canine model offers a critical insight for evaluating “whether these cell replacements—where we are introducing cones into the retinas of these dogs—is a successful approach for restoring cone vision,” says Beltran, the Corinne R. and Henry Bower Endowed Professor of Ophthalmology.

He and Gustavo Aguirre teamed with researchers including cognitive neuroscientist Geoffrey K. Aguirre, a professor of neurology at the Perelman School of Medicine, bringing together knowledge on the retinal system and brain measurements. In dogs with three different kinds of naturally occurring retinal disease and in dogs with normal vision, the scientists used functional magnetic resonance imaging (fMRI) to assess brain responses to lights that stimulate only the cone cells. 

Their findings were published in Translational Vision Science & Technology. The other co-authors are Huseyin O. Taskin, a former research specialist at Penn in the GKAguirre Lab and current graduate student at the University of Toronto, and Jacqueline Wivel, a veterinary technician. 

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