Genome Editing with CRISPR-Cas9 Prevents Angiogenesis of the Retina

Powerful new technology may lead to novel therapies to prevent vision loss, blindness in those with diseases of the retina

Boston, Mass. — A research team from the Schepens Eye Research Institute of Massachusetts Eye and Ear has successfully prevented mice from developing angiogenesis of the retina—the sensory tissue at the back of the eye—using gene-editing techniques with CRISPR-Cas9. Angiogenesis causes vision loss and blindness and is a feature of several degenerative eye conditions, including proliferative diabetic retinopathy (PDR), wet age-related macular degeneration (AMD), and retinopathy of prematurity (ROP). In a report published online today in Nature Communications, the researchers present a novel gene-editing technique to prevent retinal angiogenesis, which could lead to the development of new therapies for eye conditions marked by pathological intraocular angiogenesis. 

Despite the success of vascular endothelial cell growth factor (VEGF) inhibiting agents (e.g. Lucentis®, Eylea®) in reducing neovascular growth and lessening vascular leakage in retinal diseases such as PDR and AMD, several therapeutic challenges remain—namely a need for sustained treatment and a modality to treat the significant number of patients who do not respond to anti-VEGF therapies.

“We know that vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) plays an essential role in angiogenesis,” said corresponding author Hetian Lei, PhD, Assistant Scientist at Schepens Eye Research Institute of Mass. Eye and Ear and Assistant Professor of Ophthalmology at Harvard Medical School. “The CRISPR-Cas9 system to can be utilized to edit the VEGFR2 gene, preventing intraocular pathological angiogenesis.”

A feature of various eye diseases, pathological intraocular angiogenesis presents clinically when blood vessels in the retina (the structure in the back of the eye that senses and perceives light) begin to grow new, abnormal blood vessels on the surface of the retina. As the damage progresses, these vessels can leak, rupture, or cause retinal detachment leading to impaired vision.

CRISPR-Cas9 is a powerful new technology that can target and edit certain aspects of the genome, or the complete set of genetic material of an organism. In the Nature Communications report, study authors used an adeno-associated virus (AAV) to deliver genomic edits to target VEGFR2, a critical protein responsible for angiogenesis. A single injection of this therapy was able to prevent retinal angiogenesis in preclinical models. 

“As this genomic editing gains traction in virtually all medical fields, we are cautiously optimistic that this powerful tool may present a novel therapy to prevent vision loss in eye disease marked by intraocular pathological angiogenesis,” said Dr. Lei. “While further study is needed to determine safety and efficacy of this approach, our work shows that the CRISPR-Cas9 system is a precise and efficient tool with the potential to treat angiogenesis-associated diseases.”

In addition to Dr. Lei, authors on the Nature Communications paper include Xionggao Huang, PhD, Guohong Zhou, PhD, Wenyi Wu, Yajian Duan, Gaoen Ma, Jingyuan Song, PhD, Ru Xiao, PhD, Luk Vandenberghe, PhD, and Patricia D’Amore, PhD, of the Schepens Eye Research Institute of Mass. Eye and Ear, as well as Feng Zhang, PhD, of the Broad Institute of the Massachusetts Institute of Technology and Harvard University.

This research study was supported by National Institutes of Health/National Eye Institute grants R01EY012509 and P30EY003790.

About Massachusetts Eye and Ear 

Mass. Eye and Ear clinicians and scientists are driven by a mission to find cures for blindness, deafness and diseases of the head and neck. Now united with Schepens Eye Research Institute, Mass. Eye and Ear is the world's largest vision and hearing research center, developing new treatments and cures through discovery and innovation. Mass. Eye and Ear is a Harvard Medical School teaching hospital and trains future medical leaders in ophthalmology and otolaryngology, through residency as well as clinical and research fellowships. Internationally acclaimed since its founding in 1824, Mass. Eye and Ear employs full-time, board-certified physicians who offer high-quality and affordable specialty care that ranges from the routine to the very complex. In the 2016–2017 “Best Hospitals Survey,” U.S. News & World Report ranked Mass. Eye and Ear #1 in the nation for ear, nose and throat care and #1 in New England for eye care. For more information about life-changing care and research, or to learn how you can help, please visit MassEyeAndEar.org.

About the Harvard Medical School Department of Ophthalmology

The Harvard Medical School (HMS) Department of Ophthalmology (eye.hms.harvard.edu) is one of the leading and largest academic departments of ophthalmology in the nation. More than 350 full-time faculty and trainees work at nine HMS affiliate institutions, including Massachusetts Eye and Ear, Massachusetts General Hospital, Brigham and Women’s Hospital, Boston Children’s Hospital, Beth Israel Deaconess Medical Center, Joslin Diabetes Center/Beetham Eye Institute, Veterans Affairs Boston Healthcare System, VA Maine Healthcare System, and Cambridge Health Alliance. Formally established in 1871, the department has been built upon a strong and rich foundation in medical education, research, and clinical care. Through the years, faculty and alumni have profoundly influenced ophthalmic science, medicine, and literature—helping to transform the field of ophthalmology from a branch of surgery into an independent medical specialty at the forefront of science.