Although glaucoma is the second leading cause of blindness worldwide and affects more than 3 million Americans, little is known about its root causes. And because many cases of glaucoma do not present symptoms until the disease is advanced and causing vision loss, people who might benefit from earlier interventions often miss the chance.
To learn more about glaucoma’s origins with the hope of developing promising new treatments, researchers at the Wilmer Eye Institute are taking an innovative approach by studying the sclera, the tough, white-colored outer shell of the eyeball. Through its responses to ocular pressure — which can be but often is not elevated in glaucoma — the sclera might play an important role in glaucoma progression. Changes in the sclera’s shape and elasticity are thought to put strain on the optic nerve where it passes through a narrow hole in the sclera at the back of the eye, in turn stressing nerve cells lining the eye’s interior. This trauma can ultimately damage the neural cells and prevent visual information from reaching our brain.
While investigating the structure of the sclera around the optic nerve, a group led by Ian Pitha, M.D., Ph.D., an assistant professor of ophthalmology at Wilmer, recently made a surprising discovery involving fibroblasts, a type of cell found in connective tissue. He and a team of scientists discovered a unique pocket of scleral cells that, unlike some scleral fibroblasts, do not align themselves with the dense connective tissue that otherwise composes the sclera. “These fibroblast cells are mavericks because they don’t listen to how surrounding tissue tells them to behave,” says Pitha.
The finding is doubly intriguing because studies by other Wilmer researchers have noted increased activity by scleral fibroblasts in animal models of glaucoma. While it is too soon to know exactly what this newly described population of scleral cells is doing in glaucoma, the findings add to the growing picture that the sclera is far more dynamic — and thus possibly involved in various eye conditions — than previously realized.
“The conventional wisdom had long been that the sclera is like a piece of shoe leather and doesn’t have any cells in it,” says Harry Quigley, M.D., the A. Edward Maumenee Professor of Ophthalmology at Wilmer and a mentor of Pitha.
“As it turns out, the sclera is actually packed full of cells, but we know very little about them,” adds Pitha. “That’s why from a standpoint of basic science, identifying this new subset of scleral cells is very exciting.”
Pitha first came to Johns Hopkins on a glaucoma clinical fellowship in 2013. Since then, he has worked closely with Quigley, who himself originally came to Johns Hopkins back in 1977. The two researchers partly credit their latest discovery — along with many other advances in glaucoma and eye disease — to the cooperative, interdisciplinary environment at Wilmer and Johns Hopkins more broadly.
“Wilmer continues to attract people with strong specialties in ophthalmology and other related fields, and that adds to what everyone else here is doing,” says Quigley. The line of research associating the sclera and glaucoma, for instance, grew out of focusing on the biomechanics of the eye, work that was kick-started a decade ago when Quigley collaborated with Thao Nguyen, Ph.D., the Marlin U. Zimmerman, Jr. Faculty Scholar in the Department of Mechanical Engineering at Johns Hopkins. As a further example, Pitha, who holds a Ph.D. in pharmacology and toxicology in addition to his M.D., brings unique skills to Wilmer. His expertise could offer insights into potential drug development for eventually targeting scleral cells, opening up a promising new way to treat glaucoma, and possibly in its earliest stages.
“There are so many unmet needs in glaucoma,” says Pitha. “We’re encouraged by our results so far and will keep striving to deliver for our patients.”