Endothelin gene expression is greatly increased in the retinal tissue of a mouse model of retinopathy of prematurity, a condition that significantly affects about 1,500 infants annually, resulting in blindness in about half those babies, according to researchers at the Medical College of Georgia at Georgia Regents University.
The finding points toward a new therapy to help prevent the damage as well as a broader role for endothelin, known as a powerful blood pressure regulator, which also appears to have a role in blood vessel formation, said Dr. Chintan Patel, MCG postdoctoral fellow and first author of the study in The American Journal of Pathology.
Despite long-standing strategies to give premature newborns the lowest oxygen therapy possible to protect fragile, immature tissues such as the retina while providing adequate support to vital organs, vision damage remains an ongoing concern in neonatal intensive care units, said Dr. Jatinder Bhatia, Chief of the MCG Section of Neonatology.
In addition to immediate impacts on vision, the condition increases a child’s risk of retinal detachment, nearsightedness, crossed eyes, lazy eye, and glaucoma, according to the National Eye Institute.
The retina is part of the brain and, like the rest of the brain, it continues to develop even after full-term birth, said Dr. Ruth Caldwell, cell biologist at MCG’s Vascular Biology Center and the study’s corresponding author. The soft, three-layered tissue, found at the back of the eye, contains light-sensitive cells, which transform light into a signal for the brain.
The cup-shaped tissue is normally super vascular, but in premature babies, retinas, which are not yet ready to function, likely have not formed blood vessels throughout. Oxygen therapy, necessary to support other organs, further slows blood vessel development so the retina become ischemic. Neurons and supporting cells start secreting proteins and growth factors to try to recuperate from the lack of oxygen and nutrients to these areas, which instead, leads to formation of leaky, malpositioned blood vessels. “There is a dysregulation of growth factors that occurs at a microscopic level,” Patel said.
There are a number of other things happening at the same time, which also are not good. High-oxygen levels also increase levels of oxidative stress, which increases inflammation in the face of decreased production of growth factors needed to produce healthy blood vessels, Patel said. Blood vessels start growing in every direction, including on top of each other. “We call it pathological neovascularization,” he said.
Activation of the Endothelin System Mediates Pathological Angiogenesis during Ischemic Retinopathy, Chintan Patel, S. Priya Narayanan, Wenbo Zhang, Zhimin Xu, Sangeetha Sukumari-Ramesh, Krishnan M. Dhandapani, R. William Caldwell, Ruth B. Caldwell, The American Journal of Pathology, DOI: 10.1016/j.ajpath.2014.07.012, published online 6 September 2014.
Source: Georgia Regents University