Cobalt Toxicity Induces Retinopathy and Optic Neuropathy in Mice.

Abstract

PURPOSE: To explore the effect of cobalt toxicity on vision. METHODS: A total of 103 wild-type (WT) mice were injected with cobalt chloride by two routes in different concentrations: single intravenous (IV) high or low doses (total, n = 43); or daily repeated intraperitoneal (IP) high (three days) or low (28 days, 56 days) dose, and low-dose cobalt with added minocycline (56 days) (total, n = 60); 10 WT mice served as a control group. An additional group of 17 immunodeficient NOD scid gamma (NSG) mice were injected IV or IP with cobalt, and 10 NSG mice served as control. Cobalt levels were measured in blood, urine, and tears by particle-induced X-ray emission (PIXE). Macroscopic, immunohistochemical, electroretinography (ERG), and molecular studies were done. RESULTS: PIXE revealed cobalt elimination from the blood by two hours, with increased levels in urine but under the detection limit in tears. In the retina, ERG recordings showed decreased b-wave amplitude. Apoptosis mainly involved the inner retina, with inner retinal inflammatory reaction in both WT and less in the NSG mice. In the optic nerves, an increased microglial and astrocytic activation was noted. CONCLUSIONS: This study demonstrated functional visual impairment with extensive inflammatory reaction secondary to cobalt toxicity in mice.