New Glaucoma Mouse Model

Palo Alto, CA — Glaucoma is a common eye disease due to degeneration of the optic nerve, and eye pressure is an important risk factor. There are limited therapies since it is difficult to model glaucoma in the lab. But a collaboration between the Mahajan and Hu labs at the Byer’s Eye Institute at Stanford University has generated an important new animal model to help accelerate research to treat glaucoma.

The concept of a new glaucoma model came when Vinit Mahajan M.D., Ph.D., associate professor of ophthalmology and vitreoretinal surgeon, was operating to repair a retinal detachment that required an injection of silicon oil. In complex vitreoretinal surgery, silicon oil has improved the outcomes in eyes that would otherwise have had a poor prognosis.

Mahajan said, “Normally, the silicon oil acts as a bandage, holding the retina in place until it heals. But we have to be careful. If there is too much oil or it escapes into the front part of the eye, pressure can go up and the patient is at risk for glaucoma.”

Mahajan was describing a potential side effect of silicon oil - pupillary block glaucoma. The block originates when fluid cannot flow between the front and back of the eye, if the silicon oil covers the pupil. Then the anterior chamber becomes shallow and interocular pressure goes up. Mahajan reached out to his colleague to see if the same affect might be recreated in mice.

Yang Hu M.D., Ph.D., an assistant professor of ophthalmology at Stanford who is an expert in  glaucoma research, met with Mahajan and thought it might work. Researchers in his lab tested injections of microscopic oil bubbles into the tiny eye of the mouse. As hoped, the eye pressure went up and there was damage to the optic nerve. Next, the team performed a delicate, highly skilled procedure to remove the oil. The eye pressure decreased. The “reversible,” highly controlled nature of the new model was a first for glaucoma researchers.

Hu explained, “Because IOP quickly returns to normal, the model can be used to test the effect of lowering IOP on glaucomatous retinal ganglion cells. This method is straightforward, does not require special equipment or repeat procedures, closely simulates clinical situations, and may be applicable to diverse animal species.”

The team published their peer-reviewed manuscript, “Silicone oil-induced ocular hypertension and glaucomatous neurodegeneration in mouse” in eLife. In order to share this important model with other researchers, the team also published a “How-To” in JoVE.

Mahajan said, “Professor Hu and his lab get full credit for translating a human finding into an important research tool. They did a truly awesome job. It’s great to have smart colleagues that deliver important research results.” 

Authors of “Silicone oil-induced ocular hypertension and glaucomatous neurodegeneration in mouse”published in eLife include: Zhang J, Li L, Huang H, Fang F, Webber HC, Zhuang P, Liu L, Dalal R, Tang PH, Mahajan VB, Sun Y, Li S, Zhang M, Goldberg JL, Hu.

Authors of “A Reversible Silicon Oil-Induced Ocular Hypertension Model in Mice” published in JoVE include: Zhang J, Fang F, Li L, Huang H, Webber HC, Sun Y, Mahajan VB, Hu Y.