A team of researchers from the Schepens Eye Research Institute of Massachusetts Eye and Ear in Boston has prevented mice from developing angiogenesis of the retina by using CRISPR-Cas9 gene-editing techniques. The research, supported by NIH and NEI grants, was reported in an online article in the journal Nature Communications, and study authors say it could open the door to new methods of treating the most prevalent retinal diseases. CRISPR technology has already been widely studied as a potential approach to treating inherited retinal diseases.

"We know that vascular endothelial growth factor receptor 2 (VEGFR2) plays an essential role in angiogenesis," said corresponding author Hetian Lei, PhD, assistant scientist at Massachusetts Eye and Ear and assistant professor of ophthalmology at Harvard Medical School. "The CRISPR-Cas9 system can be utilized to edit the VEGFR2 gene, preventing intraocular pathological angiogenesis.

"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."
"Hetian's study has identified an attractive target for genome editing for AMD,” said Luk Vandenberghe, PhD, a coauthor and member of the research team at Massachusetts Eye and Ear. “Clinical translation of these and other approaches that are efficacious and safe however will hinge on further extensive development of technologies specific to editing and a deeper understanding of the genome editing biology and its limitations."

The researchers employed an adeno-associated virus (AAV) as a delivery vehicle to genomically edit VEGFR2 in mouse pups. A single injection of this therapy was able to prevent retinal angiogenesis in preclinical models. The effect of the therapy favorably compared to a control group of mouse pups that had been induced with angiogenesis but did not receive the gene-editing treatment.

“CRISPR-Cas9 gene editing holds great promise for treating an array of retinal diseases, particularly inherited retinal diseases,” said Joan W. Miller, MD. chief and chair of ophthalmology, Massachusetts Eye and Ear and Massachusetts General Hospital, Harvard Medical School. “Gene-based therapies have potential for angiogenic eye diseases like AMD and diabetic retinopathy, but these diseases are currently well controlled with anti-VEGF agents and long-term delivery strategies of these agents are on the horizon. Genome editing approaches would need to target sufficient neovascular endothelium without affecting normal retinal and choroidal vessels, and this may be a difficult hurdle. Genome editing in inherited retinal diseases may offer greater opportunity.”

Regarding research using gene editing in inherited retinal diseases, Allergan has an agreement with the gene-editing company Editas that initially targets the gene mutation that causes Leber’s congenital amaurosis, and researchers at the University of California San Diego and also at Columbia University (in collaboration with the University of Iowa) are studying the potential of using gene editing as a therapy for inherited retinal diseases.