Intravitreal chemotactic and mitogenic activity. Implication of blood-retinal barrier breakdown

Abstract

We produced breakdown of the blood-retinal barrier (BRB) in pigmented rabbits by several different mechanisms: retinal cryopexy, retinal laser, intravenous sodium iodate (30 mg/kg), or intravitreal injection of epinephrine (0.1 mL, 10(-3) M). The degree of BRB breakdown was monitored by computerized vitreous fluorophotometry. At 72 hours after treatment, rabbits were killed, and eyes were quickly removed, washed, and placed in liquid nitrogen. The vitreous was then carefully isolated free of contamination from other ocular tissues, homogenized, and aliquotted. For each sample we measured protein content, retinal pigment epithelial (RPE) cell chemotactic activity, and RPE mitogenic activity. Each of the above modalities produced significant breakdown of the BRB as measured by vitreous fluorophotometry and intravitreal protein concentration, while a pars plana intravitreal injection of saline (0.1 mL) did not. Vitreous from eyes treated with each of the above modalities caused significant stimulation of RPE migration (cryopexy, 684%; laser, 211%; sodium iodate, 480%; intravitreal epinephrine, 546%), while control vitreous and saline-injected vitreous caused only 89% and 77% stimulations, respectively. Similarly, vitreous from eyes treated with the above modalities caused significant stimulation of RPE proliferation (116% to 159%), while control vitreous caused only a 56% increase above baseline. Proliferative vitreoretinopathy, a disease process in which cellular migration and proliferation play important roles, occurs most commonly after surgical intervention. Breakdown of the BRB at the time of surgery may be a critical event due to intravitreal accumulation of serum-derived chemoattractants and mitogens.