When you get a paper cut, after about two weeks the skin repairs itself and you can’t see where the cut was located.
If something similar should happen to your retina, you’re out of luck. Unlike skin cells, the cells of the retina don’t regenerate. So, if it is damaged in any way, the cells form scar tissue instead dividing to promote regeneration. The end result is blindness.
Yet, that is only true with mammals. There is a fish, the zebrafish, which has the ability to regenerate damaged retina cells and restore its eyesight within three weeks of an eye injury. How does it do that and can this be applied to humans? Researchers both the U.S. and Belgium want to answer this question.
A group headed by Lieve Moons at the University of Leuven, Belgium, found that a group of enzymes, known as matrix metalloproteinases (MMPs), work together to help the retina reconnect with the brain after optic nerve damage. To regain sight, the neurons of the retina must regrow its axons through the optic nerve and make new connections with the brain. The lab at the University of Leuven wanted to establish a timeline for the MMP activity.
They examined the damaged optic nerves of the fish over the course of three weeks and found the most changes occur in two MMPs during the first week of recovery, namely MMP-13a and MMP-2. The lab theorized that if they blocked MMP activity in the first week of recovery, then the axons would not regrow.
They repeated the experiment and this time they injected either saline or a MMP inhibitor, as well as a biomarker in the fish to see if the axons regenerated. When they checked the fish again, they saw less of the biomarker in the brains of the fish injected with the MMP inhibitor when compared to the fish injected with saline. From this, we can conclude that MMPs are critical for regaining vision in zebrafish.
A group at Notre Dame University are studying zebrafish as well, and they identified thousands of genes that are involved in repairing retinal damage. They also found that when they killed certain eye cells in the fish, only specific types of cells would regenerate in their place.
The Notre Dame group did an experiment in which they damaged a zebrafish’s retina, isolated the proteins from that retina, and then injected these proteins into a healthy fish’s eye. The thinking was that this would induce a regeneration response in a healthy retina.
This experiment identified several molecules. One in particular is the Tumor Necrosis Factor Alpha (TNF-alpha) that appears early in the injury response but wasn’t showing up in the microarray study. This molecule is produced in dying photoreceptor cells and it plays a role in initiating the repair response. In other words, the dying cells release the molecule, other cells recognize the release, and the repair process starts.
Of course, it will be many years, before work done with zebrafish can be adapted to for use in humans. Still, the results are very promising. After all, once cells in the retina are regenerated and wired to the visual cortex, vision is restored.