Glaucoma research has long been hindered by the inability of scientists to induce glaucoma while continuing to control eye pressure. Fortunately, in a recent study published in Scientific Reports, an innovative model, conceived and tested by scientists at the University of South Florida (USF) has overcome that challenge.* 

Background

Until this study, all animal-based glaucoma studies involved inducing glaucoma-like symptoms by blocking the outflow of aqueous humor (fluid that bathes and nourishes the eye) through the eye’s trabecular meshwork (drainage pathway). 

The chronic buildup of fluid inside the eye results in patterns of retinal and optic nerve injury like that seen in glaucoma patients. This method mimics open-angle glaucoma in humans—the most common form of glaucoma among adults in the U.S.

Important limitations of this model include:

• varying intraocular (internal eye) pressure of each animal; 
• permanent intraocular pressure (IOP) changes that vary in degree over time; and
• permanent aqueous outflow damage, limiting scientists’ knowledge of the eye’s ability to recover from the induced symptoms.

The number of variable factors that influenced results from these studies limited their usefulness both as a base for new treatments and a jumping-off point for further research.

What they did

This USF study introduced an infusion-based model of glaucoma. This was accomplished by implanting a cannula in one eye of 28 Brown-Norway rats. Each cannula was connected to a pressure sensor, and a saline fluid reservoir with a pump served as a pressure source. The rats were given time to recover from the surgery, then allowed to move freely, the tube fixed in place.

Without blocking the rats’ eye drainage pathways, researchers were able to use the tethered device to directly control IOP, increasing and decreasing it as needed. They increased it by 10 mmHG for up to two months, and the sensor took pressure measurements every few seconds around-the-clock during that time. No alteration was made to the control group. 

What they found

The study authors found that raising the pressure of an otherwise healthy eye resulted in patterns of retina and optic nerve damage like those seen in human glaucoma, but there were differences, as well.

Results of the experiment included the following:

• Optic nerves showed progressive degeneration over the course of exposure.
• Retinal damage did not occur without the sustained elevation of IOP.
• Normal outflow ability of the affected eyes remained unchanged. 
• Resting IOP was unaffected despite the severe optic and retinal nerve damage.
• No evidence of cellular remodeling of eye drainage pathways occured in response to the increased eye pressure.

What this means

Taken together, the study’s findings show that chronic IOP elevation is sufficient to cause optic nerve degeneration and the death of retinal ganglion cells (RGC), the hallmark of glaucoma.

That aqueous drainage pathways continued to function normally was unexpected, however. In human glaucoma, changes in extracellular matrix properties and cell mechanobiology cause trabecular (drainage) tissue to stiffen, and that stiffening is thought to increase IOP by hampering outflow. 

The question of what initiates and drives that process remains unanswered. One theory holds that glaucoma results from a malfunction of the eye’s homeostasis, the system by which an organism or cell attempts to regulate its internal conditions to maintain stable health and function. 

According to Chris Passaglia, Ph.D., a professor of medical engineering at USF and co-author of the study, the new infusion-based model may pave the way for scientists to find that answer sooner rather than later by overcoming the limitations of previous studies. “Now researchers can have direct knowledge and control of eye pressure,” said Passaglia. “The technique offers a significant advancement in glaucoma research.” 

For more information, you can read the full study in Scientific Reports and check out USF’s press release.

*Ficarotta, K.R., Mohamed, Y.H., Passaglia, C.L. (2020, Jan. 10). “Experimental glaucoma model with controllable intraocular pressure history.” Scientific Reports.

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