Abstract
Purpose: :
The presence of "plus disease" is the critical factor for identifying infants who require treatment for severe retinopathy of prematurity (ROP). Plus Disease is defined as retinal vessels abnormality with high degree of arterial tortuosity and venous dilation. However, the evolution and pathogenesis of these vascular changes are largely unknown. We aim to better understand disease progression and develop a quantitative method for diagnosing vascular abnormalities in ROP
Methods: :
Retinal neovascularization and vessel tortuosity were evaluated using the oxygen-induced retinopathy (OIR) mouse model. Mice were subjected to 75% oxygen from post-natal day 7 (P7) to P12 and returned to room air until P17. The resulting relative hypoxia triggers a proliferative response in the retinal vasculature that resembles ROP in human patients. The retinal vascular changes were analyzed by fundus angiography and retina flat mount staining with isolectin B4, a marker for endothelial cells that delineates blood vessels, or for incorporation of 5-bromo-2-deoxyuridine (BrdU) staining as a marker for cellular proliferation
Results: :
The retina of mice subjected to the OIR model developed a significant avascular area after been exposed to high concentration of oxygen. During the subsequent 5 days in normoxia (P17), the major vessels that remain in the avascular area became progressively more tortuous and dilated, as assessed by whole mount analysis. Vessel tortuosity developed in a time dependent manner and became apparent at P15, reaching a maximun at P18-19. The tortuosity appears to be caused by proliferation of endothelial cells, as evidenced by BrdU incorporation
Conclusions: :
Plus disease in patients is usually only evaluated at one or two time points, and so the development of a mouse model allows an evaluation of the progression of this disease and identification of different stages. Our results suggest that plus disease is caused by proliferation of endothelial cells, providing a conceptually novel explanation for the development of vessel tortuosity and dilation, both key characteristics of plus disease
Keywords: neovascularization • proliferation • retina