Hyperoxia‐Induced Preretinal Membrane Formation and Retinal Detachment in the Mouse

Abstract

BackgroundRetinal detachment (RD) is a vision‐threatening consequence of several conditions including retinopathy of prematurity (ROP). Numerous studies have established the connection of high oxygen concentration altering retinal development in preterm infants, leading to RD and blindness in later stages. The goal of this study was to develop a reproducible, non‐invasive model mouse of human ROP that could be used to study the cellular events leading to the formation of tractional preretinal membranes and RD.HypothesisPlacing C57BL/6J mice in hyperoxic conditions for one week starting at birth will induce a non‐traumatic sequence of retinopathy leading to tractional RD that mimics the pathophysiology of detachment seen in ROP.MethodsC57BL/6J newborn mice were placed into a hyperoxic environment (65% oxygen saturation) for 7 days then reared in ambient air. Retinas were observed at weeks 4, 5, and 7 via spectral‐domain optical coherence tomography (OCT). Eyes were processed for histology and immunostaining for the myofibroblast marker alpha‐smooth muscle actin (α‐SMA).ResultsFour weeks after birth, 100% of mice placed in hyperoxia exhibited retinal blebs, 91% had developed preretinal membranes, and 9% had RD. At 5 weeks, 100% and 27% had preretinal membranes and RD, respectively. At week 7, the number of mice with RD increased to 33%. Preretinal membranes arose at the surface of the retina above the optic nerve head. RD occurred between the neurosensory retina and the underlying retinal pigment epithelium. Myofibroblasts were detected with the antibody to α‐SMA in the preretinal membranes and above areas of RD.ConclusionThe hyperoxia‐induced retinopathy model was confirmed to induce retinal pathology in newborn mouse pups. Retinal pathology progressed during a 7‐week time period (i.e. retinal blebs to preretinal membranes and folds to retinal detachment). This noninvasive model replicates the oxygen‐induced retinopathy seen in human ROP. The model is useful for investigating the origin of cells that contribute to the formation of tractional retinopathy, especially PRMs and RD. The presence of α‐SMA‐positive cells overlying areas of retinopathy suggests the contractile property of myofibroblasts induces tractional RD.