About three million Americans have glaucoma and it is the second leading cause of blindness worldwide. Treatments for adults may include eyedrops, oral medications, and other options including laser therapy and various surgical procedures. There are no cures, and a severe form of glaucoma in children between birth and three years old known as primary congenital glaucoma can only be treated with surgery. Researchers are actively searching for new therapeutic targets. Now, researchers at Northwestern Medicine report  new potential treatment targets for glaucoma in mice, including preventing a severe pediatric form of glaucoma, and a possible new class of therapy for the most common form of glaucoma in adults.

The findings are published in the journal Nature Communications in a paper titled, “Cellular crosstalk regulates the aqueous humor outflow pathway and provides new targets for glaucoma therapies.”

“Primary congenital glaucoma (PCG) is a severe disease characterized by developmental defects in the trabecular meshwork (TM) and Schlemm’s canal (SC), comprising the conventional aqueous humor outflow pathway of the eye,” the researchers wrote. “Recently, heterozygous loss of function variants in TEK and ANGPT1 or compound variants in TEK/SVEP1 were identified in children with PCG. Moreover, common variants in ANGPT1and SVEP1 have been identified as risk alleles for primary open angle glaucoma (POAG) in GWAS studies. Here, we show tissue-specific deletion of Angpt1 or Svep1 from the TM causes PCG in mice with severe defects in the adjacent SC.”

“Although primary congenital glaucoma is much rarer than open angle glaucoma, it is devastating for children,” explained corresponding author Susan Quaggin, MD, chief of nephrology and hypertension in the department of medicine at Northwestern University Feinberg School of Medicine. “New treatments and new classes of treatments are urgently needed to slow vision loss in both forms.”

Using gene editing, the scientists in the study developed new models of glaucoma in mice that resembled primary congenital glaucoma. The researchers injected a new, long-lasting and non-toxic protein treatment (Hepta-ANGPT1) into mice, to replace the function of genes that, when mutated, cause glaucoma.

The researchers observed they were able to prevent glaucoma from ever forming in one model. The same therapy, when injected into the eyes of healthy adult mice, reduced pressure in the eyes, which holds potential promise for the most common cause of glaucoma in adults (high intraocular pressure open angle glaucoma).

The researchers are looking forward to developing the appropriate delivery system for the successful new protein treatment in patients and bring it to production, Quaggin said.

“Our hope is that this study leads to the first targeted therapy that effectively promotes (aqueous humor) fluid outflow from the front of an eye, reversing the underlying biologic defect in patients with glaucoma.”