Gene therapy of twilight blindness
Leber congenital amaurosis (VAL) is one of the most common causes of congenital blindness, affecting approximately one in 40,000 newborns. The degree of vision loss may vary in different patients with VAL, but all such patients are sick from the first months of life. There are more than two dozen genes whose dysfunction can cause VAL.
Up to 20% of VAL cases are caused by mutations in the GUCY2D gene, which encodes retinal guanylate cyclase 1, an enzyme necessary for the phototransduction cascade in retinal photoreceptor cells – a process that converts a light pulse into neural signals. Previous studies have shown that patients with this form of VAL tend to have relatively preserved photosensitive cells, especially in areas rich in rods, indicating that rod-based phototransduction could work again if the functional protein GUCY2D was present. Previously, the results of low-dose gene therapy, which were reported last year, confirmed this hypothesis.
Two patients (a 19-year-old male and a 32-year-old female) with mutations in the GUCY2D gene participated in a clinical study organized by the staff of the Sheye Eye Institute at the Perelman School of Medicine at the University of Pennsylvania. In daylight, they retained some visual functions, but at night they were practically blind, and the photosensitivity was about 1000-10000 times less than normal.
The researchers injected vectors based on adenoassociated viruses that carried the DNA of a healthy version of the gene into the retina of one eye of each of the patients so that it could be compared with an untreated eye and evaluate the effect. The operation on the retina was performed by Allen K. Ho, MD, Professor at Thomas Jefferson University. Within a few days after treatment, each patient had a significant increase in visual functions mediated by rod photoreceptors. The sticks are extremely sensitive to light and provide a person's ability to see in low light conditions.
Tests showed that after therapy in both patients, the eyes became thousands of times more sensitive to light in low-light conditions, which significantly corrected the initial vision deficit.
The researchers used a total of nine additional methods to measure the light sensitivity of patients' eyes and functional vision. They included checking the skills of navigating around the room in low light conditions and checking the reaction of pupils to light. The tests invariably showed significant improvements in vision in low light, patients also noted functional improvements in their daily lives, noting that it turns out, for example, to see objects and people in the dark
Equally surprising was the rate of improvement after therapy. Within eight days, both patients had already demonstrated instrumentally measurable progress.
Thus, gene therapy restores the functions of rod-based photoreceptors, and patients with more severe rod dysfunction are likely to benefit most from treatment.
The practical message of the study is that if a SHAFT is suspected, special attention should be paid to measurements of twilight vision to assess the work of the retinal rod photoreceptors.
The results of the study also show that in some patients with severe congenital blindness, the sensitive retinal cells that provide vision remain mostly intact, the molecular mechanism of phototransduction does not suffer to a large extent and only the replacement of the missing protein is required for the cells to start functioning again more or less effectively even after decades of blindness.
Article by S.G.Jacobson et al. Night vision restored in days after decades of congenial blindness is published in the journal iScience.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru Based on Neuroscience News: Gene Therapy Rapidly Improves Night Vision in Adults With Congenital Blindness.