Regeneration in the Retina

The human body has an amazing ability to heal itself. If you get a paper cut, the cut heals in seven to ten days. If you get a bruise, it heals within two to four weeks. If you get a broken bone, it takes three to ten weeks to heal. An injury to the retina doesn’t follow the healing time span of skin and bone. When the retina is damaged after blunt injury, treatment needs to take place shortly after the injury. If the injury is due to disease, like retinitis pigmentosa or age-related macular degeneration, a person is out of luck and unfortunately has to deal with diminishing vision.

…Or maybe not. Research done at the National Eye Institute (NEI) shows that it may be possible to reduce vision loss by temporarily eliminating immune cells called microglia. This research opens up the potential for therapies that control inflammation and slow the progression of retinitis pigmentosa and age-related macular degeneration.

When a retina is healthy, the communication between the microglia and the neuron enables the neuron to send signals to the brain. When the retina is injured, the microglia travel to the injury site to remove unhealthy or dying cells. During this healing process, however, they can also remove healthy cells, which can lead to vision loss. Other studies have shown that with diseases like retinitis pigmentosa and age-related macular degeneration, removing the microglia can preserve healthy photoreceptor cells and slow vision loss. But wait, isn’t the microglia important for the retina’s neurons? So, what do you do in situation like this? That’s where new research comes in.

Wai T. Wong, M.D., Ph.D., chief of the NEI Section on Neuron-Glia Interactions in Retinal Disease and the study’s lead investigator wanted to see what happens in the retina when the microglia are eliminated. He was interested in seeing if the cells would go back to their usual arrangement and perform their normal function. To test this, his lab used the drug PLX5622, also known as Plexxikon, to eliminate microglia in mice. This drug blocks the microglial CSF-1 receptor. The microglia need signals from this receptor for their survival. Interrupting this signal for a few days caused them to disappear, except for a few cells that gathered around the optic nerve.

Loss of microglia for a short period of time doesn’t affect the neurons, therefore, removing the microglia could be used as an intervention to reduce inflammation. You can think of this like hitting the pause button on the retina’s immune system while healing functions are going on in the eye. Dr Wong found that within 30 days of stopping Plexxikon, the microglia increased in number and within 150 days the number of microglia returned to normal.

Dr Wong’s team also measured the retinal neuron’s electrical signals by way of electroretinography (ERG). They found that after the cells were stimulated by light, the microglia were able to communicate and maintain the function of the neurons in the retina. “The organization of these immune cells is quite elaborate, and all the organization comes right back,” Wong said. “We can actually image the eye and watch these cells divide and split and migrate as part of the repopulation response.”

Of course, more research needs to be done to learn how to best administer this drug so that it doesn’t affect healthy tissue, but early results are promising. This is yet another example of how research is both expanding our knowledge of the eye and leading to the development of new treatments.

Sources:

https://www.merckmanuals.com/home/injuries-and-poisoning/injuries-to-the-eye/retinal-detachment-caused-by-injury-to-eye

https://www.nei.nih.gov/content/immune-cells-retina-can-spontaneously-regenerate