Utilizing a nanoparticle to target immune cells in the eyes of zebrafish increased the rate of neuron regeneration after injury, according to a recent Wilmer Eye Institute study. This study builds on earlier research from Wilmer and other institutions that demonstrated that immune cells (microglia) control the regeneration of retinal cells in zebrafish and mouse models.
Using a nanoparticle to target and deliver an immunosuppressant drug to active microglia in degenerating zebrafish retinas is an effective method of dosing and stimulating regeneration of lost retinal cells, according to the latest research, which was published in Communications Biology.
Jeffrey Mumm, Ph.D., associate professor of ophthalmology and corresponding author, says, “Here we found bringing an immunosuppressive medicine directly to microglia cells enhances these effects, speeding up the regenerative process even more dramatically—about twice as fast as the drug alone.”
“The area of regenerative biology is currently looking at ways to manage human regenerative capacities in a way that is advantageous for other sections of the body. Humans can renew some tissues and cells just fine—our skin, our gut lining, the neurons in our nose we utilize for smell.”
Jeffrey Mumm, Ph.D., corresponding author.
Dexamethasone, an immunosuppressant, was first attached to the nanoparticle dendrimer, which Kannan Rangaramanujam, Ph.D., M.S., had previously developed at Wilmer. In the experiment, the nanoparticle delivered the drug payload to active immune cells in zebrafish retinas and suppressed the activity of the cells.
An adaptive optics-corrected lattice light sheet microscope, a unique imaging system that enabled the team to capture images of the zebrafish eye almost in real time, allowed the researchers to confirm that this suppression contributed to an increase in the rates of neuron regeneration.
According to Mumm, “Dendrimers provide an exquisite targeting tool by bringing medications directly to the immune system.” This enables us to modify the activity of immune cells while minimizing the adverse effects of powerful immunosuppressants. This strategy resembles utilizing a surgical blade to test the impacts of resistant concealment instead of a demo hammer.”
Mumm hopes that this research, with its emphasis on restoring vision rather than preventing vision loss, will be transformative for people with vision loss and other eye conditions. This therapeutic method still needs to be tested on mammals and eventually humans.
“People can recover specific tissues and cells fine and dandy—our skin, our stomach coating, the neurons in our nose we use for smell,” says Mumm. “The field of regenerative science is currently taking a gander at ways of controlling human regenerative limits in a manner that is helpful for different pieces of the body.”
More information: Kevin Emmerich et al, Nanoparticle-based targeting of microglia improves the neural regeneration enhancing effects of immunosuppression in the zebrafish retina, Communications Biology (2023). DOI: 10.1038/s42003-023-04898-9
