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Members of a University of Pennsylvania research team have shown that they can prevent, or even reverse, a blinding retinal disease, X­linked Retinitis Pigmentosa, or XLRP, in dogs. The disease in humans and dogs is caused by defects in the RPGR gene and results in early, severe and progressive vision loss. It is one of the most common inherited forms of retinal degeneration in man. "Every single abnormal feature that defines the disease in the dogs was corrected following treatment," said lead author William Beltran, assistant professor of ophthalmology at Penn’s School of Veterinary Medicine. "We were thrilled," said senior author Gustavo Aguirre, professor of medical genetics and ophthalmology at Penn Vet. "The treated cells were completely normal, and this effect resulted from introducing the normal version of the human gene into the diseased photoreceptor cells."

The similarities between humans and dogs, in terms of both eye anatomy, physiology, disease characteristics and positive response to this gene therapy, raise hope for a clear path to human therapies. Beltran and Aguirre collaborated with Artur Cideciyan and Samuel Jacobson at the Scheie Eye Institute, part of the University of Pennsylvania’s Perelman School of Medicine. This achievement results from more than 10 years of close collaboration between the scientists at Penn’s veterinary and medical Schools and the University of Florida. In addition to others at Penn Vet, Scheie and Florida, researchers at the universities of Michigan and Massachusetts and the National Eye Institute at the National Institutes of Health contributed to the research.

The study will be published in the journal Proceedings of the National Academy of Sciences.

The gene therapy approach used takes advantage of a viral vector - a genetically modified virus that doesn’t cause disease and is unable to divide ­­ to deliver the therapeutic RPGR gene specifically to diseased rods and cones. In the absence of treatment, these cells malfunction and progressively die. The research team has previously successfully applied a similar approach to two other heritable vision disorders that occur in both humans and dogs: Leber congenital amaurosis and achromatopsia. The present study was more challenging, as it was necessary to target both main classes of photoreceptor cells.

While the exact disease mechanism of the RPGR form of XLRP is still unknown, the researchers were able to successfully treat dogs with two different RPGR mutations. The mutations disrupt photoreceptors in different ways, but both ultimately cause them to become useless for vision. While this form of blindness is rare in dogs, it is common in humans. Patients with XLRP usually begin to lose night vision as children and become almost totally blind by middle age. This is the first proof that this condition is treatable in an animal model; a single subretinal injection administered to the diseased dogs led to functional and structural recovery. The dogs’ recovery was assessed using a variety of methods that are used clinically in patients, such as electroretinography and optical coherence tomography. The researchers feel the results are promising and relevant for translation to the clinic.

Two clinical trials testing retinal cells derived from human embryonic stem cells report positive preliminary results. A paper published recently in The Lancet says that the cells appear to be safe four months after being injected into the eyes of two blind patients, and also describes visual improvements in the patients.

This isn’t the first trial of human embryonic stem cell-based therapies, nor is it the first human data on these therapies. It is, however, the first – albeit early – data from the only ongoing clinical trial of such a treatment. One trial involves patients with 'dry' age-related macular degeneration (AMD), the leading cause of blindness in the developed world, whereas the other is focused a juvenile form of degenerative blindness called Stargardt’s macular dystrophy, neither of which are treatable.

The results reported are from the first patient from each of the two trials, both of which will eventually enroll a dozen patients. Final results are expected in 2013. The early-stage safety trials are sponsored by Advanced Cell Technology (ACT), a stem cell firm in Marlborough, Massachusetts.

The patients had one of their eyes implanted with cells called retinal pigment epithelial (RPE) cells, which were derived from human embryonic stem cells. The implanted RPE cells are meant to engraft in the retina and replace native RPE cells that have died off as a result of the disease. RPEs provide support to the light-sensing photoreceptors in the retina, and so the ultimate goal is for the new RPE cells to rescue dying photoreceptors and slow or even stop further vision loss. The team conducting the trials, led by Steven Schwartz at the University of California, Los Angeles, reports finding no safety problems with the cell implants in the two patients. They did not see signs of, for example, tumour or other abnormal growths, retinal detachments, or immune rejection of the cells.

Scientists are reporting development of contact lenses that could provide a continuous supply of anesthetic medication to the eyes of patients who undergo laser eye surgery, an advance that could relieve patients of the burden of repeatedly placing drops of medicine into their eyes every few hours for several days. Their report appeared in ACS' journal Langmuir.

Anuj Chauhan and colleagues explain that more than 1 million laser eye correction procedures are performed each year in the U.S. The surgery enables most patients to see clearly without eye glasses or contact lenses. The procedure known as LASIK is the most common type of laser eye surgery, but complications can develop if the patient undergoes trauma or is hit very hard at any time after the procedure. Photorefractive keratectomy (PRK) doesn't have this complication, and that's why it is preferred for athletes and those in the military. A downside to PRK, however, is a longer period of pain after surgery. To ease their pain, PRK patients place drops of several medications, including anesthetics, into their eyes every few hours, which can interfere with daily life and increase the risk of drug overdose. PRK patients receive a special "bandage contact lens" after surgery to help the outer layer of the eye heal.

The researchers tested whether anesthetics loaded onto this type of lens could release the drugs over time automatically. They found that adding vitamin E to the lenses extended the time of release of three commonly used anesthetics from just under two hours to up to an entire day, or a few days in some instances. The vitamin E acts as a barrier, keeping the anesthetics on the eye, right where they are needed. The researchers say that, in the future, these lenses could serve as bandage contact lenses after PRK surgery while also delivering necessary pain medications.