A study conducted by the University of Oklahoma has found that genetic differences in surfactant proteins, previously associated with lung function in premature infants, may also influence the development of their eyes and the risk of retinopathy of prematurity (ROP). ROP is a serious eye disease affecting premature babies whose retinal blood vessels grow abnormally, sometimes resulting in vision impairment or blindness.
The research, published in Pediatric Research, examined whether specific single-nucleotide polymorphisms (SNPs) in surfactant protein A and surfactant protein D are linked to ROP risk. These proteins are known for protecting premature infants' lungs from infection and inflammation, but this study explored their potential role in eye development.
"In looking at the DNA of human babies, we found four genetic variants that are specific to eye disease, two that are protective against ROP and two that increase the risk. But what makes the study unique is that they were the opposite of what occurs in the lung," said lead author Faizah Bhatti, M.D., neonatologist and professor of pediatrics at the OU College of Medicine.
Researchers controlled for factors such as gestational age and oxygen exposure to isolate the effect of genetic variation. This approach suggests that early genetic testing might eventually help identify which premature infants are most vulnerable to developing ROP. The team is continuing to investigate how these genetic differences alter protein structure and affect blood vessel growth in the retina.
"As neonatologists, we have greatly improved the way we care for premature babies," Bhatti said. "We use far less oxygen than we used to, and we try to minimize the number of infections they get. And while that has made a positive difference in outcomes for babies, ROP has continued to rise, which comes down to a baby's genetic makeup. We have to get better at identifying which babies are at greatest risk of ROP because one size doesn't fit all."
Bhatti was previously credited with discovering surfactant protein A in the eye using animal models. According to researchers, this is believed to be the first demonstration linking surfactant proteins A and D with human retinal disease.
While limited by its focus on a single NICU population and only certain genetic variants, researchers say these findings could impact understanding not just of ROP but also how abnormal blood vessel growth occurs following preterm birth. Bhatti's lab continues broader work on how inflammation, infections, and oxygen stress affect vascular development in preterm infants.
"Ultimately, we hope to apply this knowledge to blood vessels that are abnormally developing in other parts of the preterm baby," she said. "So many of the complications affecting preterm babies occur because much of the development that was supposed to happen in the uterus has been lost, including normal blood vessel growth. Many interventions necessary to keep these babies alive can add additional stressors and increase the risk of complications, such as ROP, to an already fragile system. Studying eye disease is very important, but this study will help us understand blood vessel development in preterm babies as a whole."
