SUNY researchers learn how gene mutation causes blindness

Two SUNY campuses—Upstate Medical University and SUNY Cortland—collaborating on vision research, have moved science a step closer to learning how a gene mutation destroys the vision process thus causing retinitis pigmentosa.

Retinitis pigmentosa affects one in 3,000 people and is caused by a gene mutation that damages rod photoreceptors, or light-sensing cells, in the eye. Symptoms of the disease may first appear in childhood, but decreased loss of vision occurring throughout one’s adult life often leads to diminished night vision or tunnel vision, significantly affecting one’s quality of life.

While there is no cure for retinitis pigmentosa, researchers at Upstate and Cortland have gathered new information that may help accelerate research on new treatments.

In a study published by Cell Press in the Biophysical Journal earlier this year researchers uncovered new information into what causes the outer segment of light-sensing cells to snap under pressure, which can cause blindness.

The trio of researchers participating in the study from Upstate are Barry Knox, PhD, professor and chair of the Department of Neuroscience and Physiology and professor of biochemistry and molecular biology and ophthalmology; Mohammad Haeri MD, PhD, (a member of Knox’s research team); and Aphrodite Ahmadi, PhD, from SUNY Cortland.

Ahmadi, the senior study author, said the findings provide the first theory that explains how the structural rigidity of the outer segment can make it prone to damage. “Our theory represents a significant advance in our understanding of retinal degenerative diseases,” she said.

The outer segment of photoreceptors consists of discs packed with a light-sensitive protein called rhodopsin. Discs made at nighttime are different from those produced during the day, generating a banding pattern that was first observed in frogs but is common across species. Mutations that affect photoreceptors often destabilize the outer segment and may damage its discs, leading to cell death, retinal degeneration, and blindness in humans. But until now, it was unclear which structural properties of the outer segment determine its susceptibility to damage.

To address this question, researchers examined tadpole photoreceptors under the microscope while subjecting them to fluid forces. They found that high-density bands packed with a high concentration of rhodopsin were very rigid, which made them more susceptible to breakage than low-density bands consisting of less rhodopsin. Their model confirmed their experimental results and revealed factors that determine the critical force needed to break the outer segment.

The findings support the idea that mutations causing rhodopsin to aggregate can destabilize the outer segment, eventually causing blindness.

Measuring the fragility of these photoreceptors is helpful, said Haeri. “If this is the reason for some blindness, we can come up with a treatment to increase their flexibility and prevent these rods from bending or breaking, which ultimately may save sight for individuals.”

Haeri says the next step may be to screen different drug candidates in mice to see if the photoreceptor rods can become more stable.

Knox says collaborative research, such as that done with SUNY Cortland, can accelerate such activity by tapping into the expertise available at other campus.  Knox’s work at Upstate is also part of the university’s Center for Vision Research, which collaborates not only with SUNY Downstate, but public and private colleges around the world.

“We can collaborate with researchers in different time zones or we can collaborate with experts just down Interstate 81,” Knox said, referring to work done at SUNY Cortland in this most recent study.  “In this case, the collaboration brought together a physician-trained scientist, a physicist and a molecular biologist to advance our understanding of the causes of blindness.”

—Cell Press assisted with the article

Caption: From left, Barry Knox, PhD, professor and chair and of the Department of Neuroscience and Physiology and professor of biochemistry and molecular biology and ophthalmology; Mohammad Haeri MD, PhD, (a member of Knox’s research team); and Aphrodite Ahmadi PhD, from SUNY Cortland, are collaborating in breakthrough vision research.

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