UC San Diego

Human retinal vasculopathies commonly result in breakdown of the blood retinal barrier and formation of scars on the retinal surface. The formation of rigid scar tissue creates traction on the retinal layers that can result in tearing, detachment, and complete blindness. Currently, the only treatment option for retinal fibrosis is surgical removal, an invasive procedure that lacks consistent success at treating the condition. Furthermore, an optimized animal model for retinal fibrosis has yet to be developed. The absence of an animal model severely limits the improvement of patient standard of care. This creates a strong need for a model capable of emulating the clinical progression of retinal fibrosis in a laboratory setting. Mouse models have been proven effective at modeling the angiogenic features of retinal vasculopathies. However, current models have yet to produce the long-term scarring that is also present in a variety of ischemic retinal vasculopathies. Therefore, this study focuses on the scarring and leakage induced by the long oxygen induced retinopathy (l-OIR) as it compares to the classical oxygen induced retinopathy model, referred to as the standard-oxygen induced retinopathy (s-OIR) model. This study primarily focuses on how breakdown of the blood retinal barrier contributes to disease pathophysiology. This was accomplished through an extensive set of leakage assays that follow the disease progression in the mice across an array of time points. It was observed that leakage occurs immediately upon completion of the high oxygen treatment in the l-OIR model. This leakage persists for 7 days and was no longer observed at 14 days. While the s-OIR model leads to a greater acute peak in leakage, the l-OIR model produces leakage over a longer duration as well as a defined fibrotic plaque. This difference may be due to the difference in induced disease severity across the models, with l-OIR producing retinas with more damaged vascular structures, often lacking in central veins and arteries. Furthering scientific and clinical understanding of the role that leakage and scarring play in ischemic retinal vasculopathies will allow future research into bettering the standard of care for patients suffering from such diseases.