Retinal detachment occurs when layers of the light sensitive retina peel away from the back wall of the eye. The condition can be caused by age, injury or disease, and currently, the only available treatment is surgery to manually reattach the retina.
However, even with surgery, as many as ten percent of people will ultimately suffer permanent vision loss due to a problem that has puzzled researchers for decades.
“Despite having the detachment repaired, some people will develop a severe condition called proliferative vitreoretinopathy, or PVR, which causes scar tissue to grow on the retina,” said surgeon Colleen Cebulla, MD, PhD Assistant Director of the Retina Division at The Ohio State University Havener Eye Institute. “The brain depends on the retina to transform light into electrical pulses. PVR interrupts that process, causing vison problems ranging from distorted images to total blindness.”
Though there are many theories regarding PVR formation and prevention, it is still considered somewhat of a mystery. Fueled by a desire to offer her patients better post-surgery outcomes, Cebulla and a team of scientists at Ohio State have been studying how retinal scar tissue develops in the hopes of stopping it before it can start. Supported by several KL2 grants from Ohio State’s Center for Clinical and Translational Science (CCTS), Cebulla’s research is starting to reveal some answers.
“We found more than 500 proteins that are produced following retinal detachment, many of which trigger the kind of inflammation that starts the scarring process,” said Cebulla. “By identifying those proteins that are the most active, we can begin developing experimental therapeutics that alter those proteins and hopefully either help promote tissue regeneration or inhibit scarring.”
An estimated 57,000 people in the United States experience retinal detachment each year. The lifetime risk of developing a retinal detachment is about 1/300 and it remains a significant cause of legal blindness in the US, particularly if the macula has been damaged or if PVR develops, underscoring the need for better alternatives.
“What we are learning here not only applies to retinal detachment caused by trauma, but also people who have diseases like diabetes or macular degeneration. Having a non-surgical way to prevent retinal damage or help regenerate damaged tissue would impact millions of lives,” said Cebulla.
NOVEL ANIMAL MODELS SPEED DISCOVERY
Cebulla’s identification of protein targets has been advanced significantly through the development of two novel animal models of retinal detachment.
In order to identify the target proteins, Cebulla developed a mouse model to conduct a proteomic study of how protein levels changed in response to retinal detachment. Using a technology called iTRAQ, Cebulla’s team were able to measure and monitor each individual protein to see how quantities changed over time, and then compare those to a control group.
With the target proteins identified, Cebulla then collaborated with neuroscientist Andy Fischer, PhD, at Ohio State’s College of Medicine, to develop the first ever chick model of retinal detachment. Chicks have a larger eye, making it easier for scientists to study the process of retinal detachment as well as the efficacy of experimental therapeutics versus smaller mammalian models. Unlike common mammalian models, chicks have good color vision, making their retinas rich in the type of cells found in a human eye.
“The development of new therapies for retinal detachment has been somewhat slowed by the high costs and difficulty of using smaller mammalian models,” said Cebulla. “The study of chicks offers several advantages that ultimately can help make our findings more applicable humans.”
Recently, Cebulla has started studying what happens inside the human eye after retinal detachment to supplement her observations from the animal models. During retinal detachment surgery, vitreous fluid is being collected from participating patients. Cebulla’s team will use the fluid sample, along with the patient’s blood to see how different proteins are being expressed.
Currently, Cebulla’s team has zeroed in on one protein in particular, and is testing a pharmacological agent that inhibits that protein to see if it can stop or slow the development of PVR and damage to the retina. She expects that she will have enough data to publish her next round of findings in just a few months.
“I’m hopeful that what we learn in our studies will identify a treatment that we can bring into clinical trials in the next five years, and that I’ll be able to tell my patients that I have something new that can help preserve their vision,” said Cebulla.