Copper Chelating Compound Inhibits Inflammation Associated With Ocular Laser and Light Treatment

Abstract

Purpose: : To study the effects of a copper chelator on ocular inflammation induced by photocoagulation laser treatment and broadband light exposure in an animal model.

Methods: : Nine normal Long-Evans rats were pretreated with copper chelator trientine (polyamine) at dosage of 0.5 mMol/kg/day by intraperitoneal injection for 7 days prior to photocoagulation laser treatment. Each animal underwent unilateral photocoagulation using a Coherent argon dye laser. Twelve Wistar rats underwent broadband light exposure following 5 weeks of trientine treatment (10mg per day orally). The enucleated eyes were evaluated with immunohistochemistry and light microscopy.

Results: : The retinal thickness in trientine-treated animals was significantly less than that of the control (saline treated) group. Immunohistochemical analysis revealed fewer macrophages, as identified by an antibody against ED-1, were present in the laser sites following laser treatment in trientine-treated group compared to control groups. Expression of ED-1 was mild in the exposed and treated groups, while expression of OH-1 was robust in the exposed group, and mild in the treated group. The intensity of Ox-42 staining was higher in the exposed group compared to the treated group. Expression of activated caspase-3 was mild and comparable in the exposed and treated groups.

Conclusions: : The copper chelator trientine inhibits ocular inflammation secondary to laser and light treatment in the eye. The mechanism of action appears to involve an inhibition of free radical formation by chelating copper, a potent catalyst for the generation of free radicals in tissues. The data suggests that microphages and microglia upregulation along with increased oxidative stress occur early after retinal tissue damage. These changes were minimized by treatment with trientine. The results suggest that therapeutic applications focused on reducing free radicals may be helpful in minimizing the early events of proliferative ocular diseases.

Keywords: inflammation • oxidation/oxidative or free radical damage • immunohistochemistry