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Gene Therapy for Macular Degeneration
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Gene Therapy for Macular Degeneration

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Highlights:
  • Scientists have developed a safe gene therapy alternative for retinal blindness.
  • In people with retinal blindness, medium-wavelength cone opsin (MW-opsin) is not expressed as the rod and cone photoreceptor cells are destroyed
  • To reverse this, scientists used an adeno-associated virus to target retinal ganglion cells and loaded it with the gene for a green opsin
  • After being injected into the eye, the virus carried the gene into the ganglion cells which had become insensitive to light can now once again become light sensitive again thereby restoring sight

A safe gene therapy alternative for retinal blindness has been developed by scientists at the University of California, Berkeley.

Gene Therapy for Macular degeneration

Retinal degenerative diseases like age-related macular degeneration lead to slow loss of rod and cone photoreceptors which in turn lead to blindness. People who suffer from blindness due to retinal degeneration have just one option which is electronic eye implants.

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In people with retinal blindness medium-wavelength cone opsin (MW-opsin) is not expressed as the rod and cone photoreceptor cells are destroyed. The scientists found that medium wavelength cone opsin (MW-opsin) enables vision even in dim light. Opsin is usually expressed only in cone photoreceptor cells and makes it sensitive to green-yellow light.

Prof. Isacoff (molecular and cell biology and director of the Helen Willis Neuroscience Institute) who specializes in G-protein coupled receptors in the nervous system thought that opsin would reconnect to the signaling system in the retinal ganglial cells. Prior to trying opsin, the team tried rhodopsin found in rods. The introduction of rhodopsin in mice activated the light sensitivity of the degenerated rods and cones and the mice were able to faintly detect light. However, the team found rhodopsin to be too slow and also failed to enable image and object recognition.
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The research team then used an adeno-associated virus to target retinal ganglion cells and loaded it with the gene for green opsin. After being injected into the eye, the virus carried the gene into the ganglion cells insensitive to light and made them sensitive to light thereby restoring sight.

Opsin responded 10 times faster than rhodopsin and the researchers found that 90% of ganglion cells became light sensitive. A blind mouse affected by retinitis pigmentosa regained enough sight to distinguish between parallel and horizontal lines on an iPad.

Isacoff and Flannery (molecular and cell biology and school of optometry) went one step further and tested if the mice were able to recognize three-dimensional objects. The team is further enthusiastic about refining the therapy to enable color vision and increase visual acuity.

Isacoff and Flannery said that this simple solution could have been worked out 20 years ago. The team reported the study in an article in Nature Communications.

Currently, Isacoff and Flannery are raising funds to take this successful gene therapy into human trials which they hope can be worked out in the next three years. Isacoff believes that this therapy can be successfully used in humans to restore enough vision to move around.

References:
  1. Berry, Michael H., Amy Holt, Autoosa Salari, Julia Veit, Meike Visel, Joshua Levitz, Krisha Aghi et al. "Restoration of high-sensitivity and adapting vision with a cone opsin." Nature Communications 10, no. 1 (2019): 1221. Retrieved on 20 March 2019 from


Source: Medindia

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