Mouse model of post-surgical breakdown of the blood-retinal barrier

PURPOSE: Post-surgical macular edema is an important clinical problem resulting from breakdown of the blood-retinal barrier (BRB) after surgery. This study was designed to develop a mouse model of post-surgical BRB breakdown. METHODS: Two 25-gauge needles, one for infusion and one for aspiration, were inserted through the limbus and into the lens of one eye of adult male C57BL/6 mice. The anterior portion of the lens was aspirated and the fellow eye was untreated. At several time points after surgery, the integrity of the BRB was assessed quantitatively, using [3H]mannitol as a tracer, or qualitatively, using immunohistochemical staining for albumin. RESULTS: Eyes with partial lens extraction had a significant increase in retinal vascular leakage one day after surgery, which persisted two and three days after surgery, but by five days, was not significantly different from controls. Immunohistochemical staining for albumin demonstrated that the breech in the barrier was sufficient to allow passage of a 60kDa protein into the retina, and was localized predominantly to retinal vessels. CONCLUSIONS: Partial lens extraction in mice results in BRB breakdown (primarily the inner BRB) that is highly reproducible in the severity of leakage and its time course. This provides a valuable tool for investigation of the molecular pathogenesis and new treatment approaches for post-surgical breakdown of the BRB.