Activated Protein C Preserved Retinal Function in a Model of Central Retinal Vein Occlusion

Abstract

Purpose: : Activated Protein C (APC) is a plasma serine protease which possessesanti-coagulant, anti-inflammatory and anti-apoptotic activities, as well as direct vasculoprotective and neuroprotective activities. We investigated the protective effect of APC in the retina of a Central Retinal Vein Occlusion (CRVO) rat model.

Methods: : CRVO was induced in the right eyes of Dark Agouti rats (n=30) with rose bengal-assisted laser photothrombosis. One hour after CRVO induction, 5 µl of APC (0.5 or 5 µg) was injected intravitreally to 6 eyes respectively and 2mg/kg of APC was injected intravenously to 6 rats. The same amount of vehicle was injected intravitreally or intravenously to 6 eyes and 6 rats as a control, respectively. Retinal Function was analyzed with electroretinography (ERG) at day 1, 3 and 7 after CRVO induction. After ERG evaluation, rats were euthanized and HE staining was performed to evaluate the numbers of retinal cells in the inner (INL) and outer nuclear layers (ONL).

Results: : The amplitudes of A- and B-waves of eyes treated with APC intravitreally or intravenously were significantly larger than that of each control at each time point (p<0.05). There was no significant difference between eyes treated intravitreally with 0.5 µg and 5 µg of APC. The numbers of cells (INL and ONL) of eyes treated intravitreally (0.5 and 5µg APC) and intravenously were 72.1/277.3, 72.9/300.0 and 74.3/309.8, which were significantly higher than that of each vehicle-injected control (45.8/162.1 and 44.9/156.8) (p=0.002/0.004, 0.001/<0.001 and <0.001/0.003, respectively).

Conclusions: : APC administrated either intravitreally or intravenously preserved retinal function as well as prevented retinal cell degeneration in the inner and outer nuclear layers of a rat CRVO model.

Keywords: ischemia • retina