Inherited retinal dystrophies (IRDs) involve the degeneration of our eyes’ rods and cones.* Typically, the cones start degenerating in the peripheral retina and then progress to the central retina. This can cause a decline in vision and sometimes blindness.

In knowing the pathophysiology and that one in 4,000 people may be affected by IRDs, researchers are exploring the restoration of vision through regeneration of neurons and neural connections in the eye and overall vision system, such as photoreceptors and ganglion cells.

“This goal in humans emerged from the recognition that some species already have the ability to repair damaged photoreceptors,” explains Brian Perkins, PhD, an associate staff member at the Cleveland Clinic’s Cole Eye Institute in Cleveland.

Help from the Zebrafish

Researchers applied findings from previous studies on zebrafish. When a zebrafish’s photoreceptors are damaged, molecules are released that activate Müller glial cells in the retina to transform into stem cells that are able to divide, mature, and regenerate, and thus restore rods and cones. This action occurs after acute damage, such as from light damage and mechanical injury, but it is unknown if this same mechanism occurs in fish with genetic disorders. 

Now, researchers are studying zebrafish with gene mutations so they can identify the genes that may cause retinal degeneration. For example, zebrafish with a mutated CEP290 gene have photoreceptor degeneration and other pathologies. 

Researchers impaired the zebrafish’s retinas with high-intensity light and began to see regeneration after two weeks; however, full regeneration of photoreceptors in fish with progressive degeneration caused by disease was not achieved. “This is critical, because it indicates that the disease environment somehow limits the overall capacity for regeneration,” Dr. Perkins shares.

What’s Next for the Research?

Researchers hope to better understand why regeneration is more likely after acute damage than disease. Additionally, they hope to explore:

• If the diseased retain limits full restoration of cone density
• If immune cells play a part in regeneration or in inhibiting regeneration 
• Whether the stimulation of regeneration can be done without causing additional damage

Finally, they hope to confirm these findings in mammalian models of blindness to expand the currently limited selection of therapies for IRDs.

*Charters, L. (2021, March 31). Regeneration may help restore vision in inherited retinal dystrophies. Ophthalmology Times. https://www.ophthalmologytimes.com/view/regeneration-may-help-restore-vision-in-inherited-retinal-dystrophies