Abstract
Purpose :
Visual dysfunction due to cobalt toxicity in hip implant patient is well reported but not well understood. The aim of the study was to explore the pathophysiology of visual impairment related to cobalt toxicity.
Methods :
114 wild type mice (WT, C57Bl6) were injected with cobalt-chloride in 3 different routes: single intravenous (IV) injection (high, medium, and low concentrations) n=44; single intravitreal (IVT) injection n=30, or daily repeated intraperitoneal (IP) injections (high dose/3 days, medium dose/14 days, and low dose/55 days) n=40. Immunodeficient transgenic NOD SCID Gamma mice (NSG, n=19), were also injected IVT, IP, and IV. NSG mice were euthanized after 7d, 3d, and one hour respectively. Another 10 NSG mice served as a control. WT IP injected mice underwent repeated ERG examinations and magnetic resonance imaging (MRI). Following euthenization, macroscopic, histological and immunohistochemistry evaluation was made for eyes and brain. Cobalt levels were measured in the blood, urine and tears by particle induced x-ray emission analysis (PIXE).
Results :
following IV injection, cobalt administration was lethal to mice in high doses. Lower doses were eliminated in urine within 2 hours. ERG records showed post-synaptic dysfunction. Apoptosis involved all retinal layers, but mainly the ONL. There was thinning of the retina, with preservation of RGCs. Activated microglia were detected in both WT and NSG mice. Intensive infiltration of lymphatic cells was also noted in the dura and optic nerves following IVT and IP injections. MRI showed decreased signal of IVT injected optic nerves after 7 days as compared to the fellow nerve.
Conclusions :
Cobalt induces severe inflammation of the retina and optic nerves. Chronic exposure leads to thinning of the retina and optic neuropathy. The inflammatory reaction involves microglial cells, as demonstrated in NSG mice. the brain was also affected with meningitis and encephalitis.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.