Abstract
Purpose :
Cobalt-containing hip implants can in rare cases cause retinopathy in patients. We have examined cobalt's effects in real time on the retinal structure and glia in the mouse eye.
Methods :
We examined the effects of cobalt using either an isolated retina or a mouse retinal eyecup preparation. The retina was perfused with an oxygenated Ames Ringer and time lapse imaged using either confocal or optical coherence microscopy on a modified Leica MP microscope. Cobalt (0.2-1mM), cadmium 0.2mM, nickel 0.2mM, and ATP (0.1-1mM) solutions were held in gassed wells and applied by bath application at 35oC. Test agents were applied for 10 minutes followed by a >30min wash out period. To track the microglia, an CX3CR1 GFP (green fluorescent protein) transgenic mouse was used and Z-stack confocal images were taken.
Results :
Application of cobalt (1mM) for 10min. caused a rapid increase in the subretinal space (SRS) width in the OCT B-scan which averaged 22±10% at wash out (mean ±s.d., n=6 retinas), and the SRS width continued to swell even after returning to normal Ringer. After cobalt, the width of the outer nuclear layer (photoreceptor cells) also began to slowly increase. A hyperreflective line developed at the border of the inner nuclear and inner plexiform layer. After application of 1mM cobalt, there was a 47±11% increase in the average number of microglia filopodia in the inner retina (n=4 retinas, mean ±s.d. p <0.05), while the outer retinal microglia were less affected. Application of cadmium increased the number of inner microglia filopodia similar to that seen with cobalt, while nickel had little effect. Application of 100uM ATP also increased the number of filopodia of inner microglia, while the outer microglia were less affected (n=5,6 retinas).
Conclusions :
Our results indicate cobalt application has rapid and persistent effects on the retina even after prolonged washout. Cobalt was particularly toxic causing photoreceptor swelling. After cobalt application, the number of inner retinal microglia filopodia increased in a manner similar to that seen with ATP. Although cobalt is known for inducing hypoxia dependent transcription mechanisms, our results imply there is a more rapid direct effect of cobalt ions on the photoreceptors and other retinal neurons possibly due to oxidative stress. Which ion channels allow influx of cobalt into the retinal cells is currently unknown.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.