Glaucoma is the leading cause of irreversible blindness worldwide. Loss of vision in glaucoma is caused by the death of retinal neurons that convey visual information from the retina to the brain. Currently, there is no cure for glaucoma. In recent years it has become apparent that most forms of glaucoma are inherited and the genetic factors play a key role in its onset and development. Glaucoma-causative genes appear to be very promising therapeutic targets for glaucoma treatment. Recently, it has also been discovered that the loss of the retinal neuron function could not only be slowed down but could also be reversed. Thus, it seems hopeful that not only could the glaucoma?s progress be slowed down using genetic and epigenetic approaches, but it may also be possible to reverse its progression with retinal neuron and optic nerve axon regeneration.

The investigators propose to develop a novel visible light activated CRISPR-dCas9 based epigenetic method for glaucoma treatment and the potential for vision restoration. CRISPR is a revolutionary new technology for versatile genome alterations but the high frequency of off-target activity induced by CRISPR at sites other than the intended on-target one is a major concern, especially for therapeutic and clinical applications. This problem could be solved with a light activatable version of CRISPR, which enables localized genetic alterations, limiting off-target activity only to the illuminated cells. They will develop and construct a new instrument for localized CRISPR activation with visible light. The proposed novel light activated CRISPR-dCas9 based epigenetic method for glaucoma treatment and vision restoration is transformative since the platform could have a profound impact on developing highly effective ophthalmic therapies for a wide range of retinal disorders.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

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Beth Israel Deaconess Medical Center
United States
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