UCSB makes important advances in RD studies

Santa Barbara, CA-Scientists at the University of California, Santa Barbara (UCSB), have made discoveries that could lead to improved recovery after retinal reattachment surgery and inhibition of undesirable cellular effects that lead to proliferative vitreoretinopathy (PVR).

In a recent study conducted in collaboration with Moorfields Eye Hospital and the Institute of Ophthalmology, University College, London, UCSB scientists used human retinectomy specimens obtained at Moorfields during retinal relaxing surgery for PVR to investigate glial remodeling and neural plasticity.

They were looking for the expression of different protein molecules to identify different cell types or cellular events, and their findings validated earlier work done in a feline model, said Steven Fisher, PhD, professor of Molecular, Cellular, and Developmental Biology at UCSB.

Research breakthrough

The availability of tissue samples taken from people during surgery rather than from autopsy samples was a breakthrough in their research, said another UCSB scientist, Geoffrey P. Lewis, PhD, a research biologist at the Neuroscience Research Institute. "We could correlate very much what is going on in the retina with these still-living eyes," Dr. Lewis said.

With autopsy samples, preservation techniques are variable and the history of the samples is often unknown, he added.

Studies at UCSB and elsewhere are advancing understanding of PVR, which occurs in 5% to 10% of patients who undergo successful reattachment surgery and at this time can neither be prevented nor cured, according to Dr. Fisher.

"We were really interested in whether our animal model was essentially mimicking that disease in humans, because then we have a way to study the cellular events that occur and perhaps ways either to prevent the disease or to find some kind of therapy for the disease, which can cause blindness in people," he explained.

Retinal detachment causes three significant changes, Dr. Lewis said. Photoreceptor degeneration, structural remodeling of neurons, and glial cell proliferation all occur and likely contribute to the reduced vision associated with detachment.

Photoreceptor degeneration hinders the retina's ability to detect light, while structural remodeling breaks synapses and reduces communication between neurons. And glial cell proliferation leads to PVR when glial cells grow on the surface of the retina. In turn, PVR can lead to "re-detachment" of the retina as the glial cells grow and contract, Dr. Lewis said.

In addition, growth of glial cells on the photoreceptor surface can cause subretinal fibrosis, which prevents regeneration of photoreceptors following reattachment surgery.

The collaborative research demonstrated that all of these features, which had been observed in the feline retina, could also be found in the human retina. Drs. Fisher, Lewis, and colleagues reported their findings in the January 2005 issue of Investigative Ophthalmology and Visual Science.

Neuronal, glial remodeling

"Data reported in that study indicate that the return of good vision following successful reattachment surgery may depend on the extent of neuronal and glial remodeling that has occurred while the retina was detached," Dr. Lewis said.

Since the results validated the animal model of detachment, it is highly likely that experimental therapies that reduce cellular damage in animals will also be successful in humans, he added.

He and his colleagues continue to conduct experiments with one form of therapy involving changes in oxygen levels.

According to Dr. Fisher, the architecture of the eye puts the circulation of photoreceptors some distance away from the cells. "Our hypothesis was that when a retinal detachment happens, one of the things it does is physically move the photoreceptors farther away from their source of oxygen. Maybe they are starved for oxygen, and that is why they degenerate," he said.