Summary: Gene therapy enables amazing night vision recovery in those with Leber Congenital Amaurosis.
source: University of Pennsylvania
Adults with a hereditary form of childhood blindness experienced an astonishing recovery in night vision within days of receiving the experimental gene therapy, according to researchers at the Scheie Eye Institute at the University of Pennsylvania’s Perelman School of Medicine.
The patients had Leber Congenital Amaurosis (LCA), which is congenital blindness caused by mutations in the GUCY2D gene.
Researchers whose results were published in the journal iSciencethey delivered the AAV gene therapy, which carries the DNA of the healthy version of the gene, into the retina of one eye per patient according to a clinical trial protocol.
Within days of treatment, each patient showed significant increases, in the treated eye, in visual function mediated by rod-type photoreceptors. Rod cells are extremely sensitive to light and account for most of the human ability to see in low light.
The study’s lead author, Samuel G. . , professor of ophthalmology at Penn.
LCA is one of the most common conditions of congenital blindness, affecting 1 in 40,000 newborns. The degree of vision loss can vary from one LCA patient to another but all of these patients have severe visual impairment from the first months of life. There are more than twenty genes whose dysfunction can cause LCA.
Up to 20% of cases of LCA are caused by mutations in the GUCY2D gene, a gene that encodes a key protein required in retinal photoreceptor cells for the ‘phototransport chain’ – the process that converts light into nerve signals.
Previous imaging studies have shown that patients with this type of LCA tend to retain relatively preserved photoreceptor cells, especially in the rod-rich regions, suggesting that rod-based phototransduction could function again if functional GUCY2D is present. Early results with low-dose gene therapy, which were reported last year, were consistent with this idea.
The researchers used higher doses of the gene therapy in two patients, a 19-year-old man and a 32-year-old woman, who had particularly severe vision impairment due to a rod. In daylight, patients had some visual function, albeit significantly impaired, but at night they were effectively blind, with sensitivity to light 10,000 to 100,000 times lower than normal.
The researchers administered the treatment to only one eye in each patient, so that the treated eye could be compared to the untreated eye to measure the effects of the treatment. Retinal surgery was performed by Allen C. Ho, Professor of Ophthalmology at Thomas Jefferson University and Wales Eye Hospital.
Tests revealed that in both patients, the treated eye became thousands of times more sensitive to light in low-light conditions, significantly correcting the original visual deficit. In all, the researchers used nine complementary methods to measure the patients’ light sensitivity and functional vision. This included a test of room navigating skills in low light conditions and a test of the pupil’s involuntary responses to light.
Tests consistently showed significant improvements in rod-based vision, and in low light, patients also noted functional improvements in their daily lives, such as “can” [now] Make things and people in the dark.”
What was striking was the rapid improvement after treatment. Within eight days, both patients already showed measurable efficacy,” said study co-author Artur V.
For the researchers, the results confirm that GUCY2D gene therapy restores rod-based photoreceptor function—and suggest that GUCY2D-LCA patients with severe penile dysfunction are likely to benefit significantly from the treatment.
The practical message is that there should be a focus on penile vision measurements when examining LCA candidates and in monitoring them throughout the treatment trial.
The findings also underscore the remarkable fact that in some patients with severe congenital vision loss, the retinal cell networks that mediate vision remain largely alive and intact, needing only to resupply the lost protein to start working again, the researchers said. or less immediately.
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“Night vision restored in days after decades of congenital blindnessWritten by Samuel G. Jacobson et al. iScience
Night vision restored in days after decades of congenital blindness
Vision signals to the brain begin with the cascade of light transmission in the retina
It converts visible light from the environment into chemical changes. double vision
It results when mutations disrupt the proteins of the photosynthetic transport chain.
Severe hereditary Leber blindness (LCA), Leber (LCA), is caused by mutations in the GUCY2D gene, resulting in a molecular defect in the production of cyclic GMP, the second messenger of phototransduction.
We studied two patients with GUCY2D-LCA who were undergoing gene augmentation therapy. Both patients had significant photoreceptor-based night vision deficits prior to the intervention.
Within days of treatment, the vision of the penis in both patients changed dramatically; The improvements in visual function and functional vision in these hyperresponsive patients reached >3 log10 units (1000-fold), approaching that of a healthy penis.
Rapid activation of complex molecular pathways from photoreceptors in the retina to the visual cortex and behavior is possible in patients even after they have been disabled and inactive for decades.