23 January 2013

New Observation on the Role of Rhodopsin and Retinal Degenerative Diseases

New observation on the behavior between rhodopsin and photoreceptor cells could help explain retinal degenerative diseases and find new ways to treat blindness.

Retinal degenerative diseases refers to diseases that causes the retina, the light-sensitive layer of tissue, lining the inner surface of the eye, to deteriorate. As it deteriorates, cells of the retina starts to die.

Of the cells affected by retinal degeneration, the photoreceptor cells are most important. Photoreceptor cells are neurons that convert light stimuli into signals for the brain to process.

Neurons are unlike some other cells as they do not divide or multiply. Damaged or dead photoreceptor cells can cause vision impairment and even blindness.

How photoreceptor cells die is still under study. It is believed that the biological pigment in photoreceptor cells of the retina called rhodopsin may have something to do with it. Rhodopsin is extremely sensitive to light, enabling vision in low-light conditions, and is responsible for triggering the eye to see light.

Photoreceptor Cells and Rhodopsin

Light-sensing cells in the eye rely on their outer segment to convert light into neural signals that allow us to see. But because of its unique cylindrical shape, the outer segment is prone to breakage, which can cause blindness in humans. A study published by Cell Press on January 22nd in the Biophysical Journal provides new insight into the mechanical properties that cause the outer segment to snap under pressure. The new experimental and theoretical findings help to explain the origin of severe eye diseases and could lead to new ways of preventing blindness.

"To our knowledge, this is the first theory that explains how the structural rigidity of the outer segment can make it prone to damage," says senior study author Aphrodite Ahmadi of the State University of New York Cortland. "Our theory represents a significant advance in our understanding of retinal degenerative diseases."

Video: Mutant Opsin Aggregates in Rod Photoreceptor Outer Segments

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, Ahmadi and her team 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. "Further refinement of the model could lead to novel ways to stabilize the outer segment and could delay the onset of blindness," says Ahmadi.


Cell Press
Biophysical Journal
State University of New York at Cortland
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