$2.3 Million NIH Grant Furthers Research Into Retinopathy of Prematurity

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OKLAHOMA CITY – A University of Oklahoma neonatologist and researcher has earned a five-year, $2.3 million grant from the National Institutes of Health to further her studies on retinopathy of prematurity, a serious eye disease that can affect babies born prematurely and cause lifelong complications, including blindness.

Faizah Bhatti, M.D., earned the grant on the strength of her ongoing studies into retinopathy of prematurity (ROP), which occurs because the premature baby’s retinal blood vessels do not have time to develop properly in the womb. She was the first researcher to discover the presence of a key immune protein in the eye (surfactant protein A) that is closely linked to blood vessel growth and was previously thought only to exist in the lungs. Her new grant will allow her to investigate what the protein is doing as ROP develops, ultimately leveraging that knowledge in the hopes of designing a prevention for the disease. ROP is the leading cause of acquired childhood blindness in the United States.

“Through advancements in medicine, we can now save babies who are born as early as 22 or 23 weeks, but when that occurs, much of the development that was supposed to happen in the uterus has been lost, including normal blood vessel growth. When a baby is born at the full nine months of gestation, the retina should be nearly covered in blood vessels for normal functioning. When a baby is born at six months, the retina has only the first small buds of blood vessel development. Sometimes babies have mild ROP that goes away on its own, but in other babies, the blood vessels develop so abnormally that the shape of the retina is distorted and can detach,” said Bhatti, an associate professor of pediatrics, ophthalmology and neurosciences in the OU College of Medicine.

Babies born prematurely face a multitude of stressors, and they often require high amounts of oxygen to survive, which can increase the risk of ROP. However, even as physicians have become more skilled at keeping oxygen levels in a safe range, ROP has continued to rise. That led Bhatti to focus her research on other factors contributing to the condition.

Previously, she published a seminal paper about her discovery of surfactant protein A in the retina. Surfactant protein A is needed for blood vessels to grow normally in the eye, but in prematurely born babies, something occurs to make the protein support abnormal blood vessel growth. Bhatti’s research demonstrated that by deleting surfactant protein A in a mouse model of ROP, the eye disease was significantly reduced.

“ROP occurs in two phases,” she said. “The first is a loss of normal blood vessels in the retina, and the second is the overgrowth of abnormal blood vessels. We want to understand how this protein works so we can try to rescue the loss of normal blood vessels early in the disease process.”

After her success studying surfactant protein A in mice, she began exploring the protein in human babies born prematurely. In that study, which she is preparing to publish, she and her team characterized the genetic “signature” of the protein, providing another layer of knowledge. It is believed to be the first study illustrating surfactant protein A in human retinal disease.

Preventing ROP is important because current treatments are inadequate and, in some cases, do harm. Laser therapy can burn the abnormal blood vessels to stop their growth, but it leaves a permanent scar that prevents a portion of the retina from functioning. A second treatment involves injecting compounds into the eye to slow abnormal blood vessel growth, but the treatment also targets normal blood vessel growth, causing additional problems even though the eye may be saved.

Historically, neonatal research has focused on the major prematurity complications that determine whether a baby lives or dies, such as lung development and resuscitation. As the field has improved in those areas, research into diseases like ROP is increasing. That is important to Bhatti, who was trained both in the clinical care of premature infants and in the scientific study of diseases related to the growth of the fetus and infant.

“This type of research is crucial because eye disease will have a major impact on these infants for the rest of their lives,” Bhatti said. “They are at greater risk for neurodevelopmental disabilities and for adult eye diseases. Eye disease affects quality of life and a person’s ability to integrate into society.”

Bhatti’s findings may be applicable to other organs affected by prematurity. As director of the Developmental Vascular Biology Lab within the OU Health Center for Pregnancy and Newborn Health, her lab focuses more broadly on normal and abnormal blood vessel growth.

“Whatever is happening in the eye is not happening in isolation,” she said. “We can use the knowledge we gain from studying ROP and apply it to systems like the brain, the lung and the gut to better understand other complications of prematurity that are linked to abnormal blood vessel development.”

Bhatti is also preparing the next generation of researchers for that work. “After the first few weeks of my rotation in Dr. Bhatti’s Developmental Vascular Biology Lab, I knew I had found an extraordinary place where I would be pushed to meet a high standard of scientific rigor while being supported and encouraged to be myself,” said doctoral student Riley Van Trease. “Visiting the NICU and seeing the tiny patients for whom we are working to find better treatments really brings into perspective the overarching focus of our work in the lab: to improve outcomes for babies. I feel very grateful to be able to conduct my Ph.D. studies on the impact of surfactant protein on retinal vascular development under the mentorship of Dr. Bhatti.”