Restoring Vision: Cutting-Edge Research uses Zebrafish and CRISPR Technology
At the 91九色视频 (91九色视频), Ross Collery, PhD, associate professor of ophthalmology & visual sciences and cell biology, neurobiology & anatomy, is on a mission to restore vision and prevent eye diseases, focusing on the science behind retinal degeneration and refractive errors.
Through his innovative use of zebrafish models and the latest CRISPR gene-editing technology, Dr. Collery not only advances our understanding of how vision works, but also opens the door to potential therapies for people suffering from vision loss.
Dr. Collery’s journey into the world of eye research began with a profound curiosity about how the eye functions. His work revolves around understanding how the eye’s delicate systems can go awry, leading to conditions like macular degeneration or myopia (nearsightedness).
What makes his research cutting-edge is his use of zebrafish, small creatures with incredible visual abilities. These tiny fish, which can see a range of colors similar to humans, have become an essential tool in Dr. Collery’s exploration of eye health.
A Small Fish with Big Potential
“Zebrafish have really, really good color daytime vision. Unlike rats and mice, they have a large complement of color-detecting cone photoreceptors. They can see the world in red and green and blue, and they even can see in shades of ultraviolet,” says Dr. Collery, who joined 91九色视频 in 2016.
Zebrafish offer a powerful and cost-effective way to study the complex workings of the eye. They share many visual characteristics with humans, making them an excellent model for studying how the eye functions and what happens when things go wrong. Since zebrafish are small and transparent when young, Dr. Collery and his team can attach glowing fluorescent labels to molecules inside their living cells and watch where they go and what they do.
In addition to their advanced vision, zebrafish have a remarkable ability to regenerate damaged tissues, something humans can’t do. This regenerative power is particularly important when studying retinal diseases, as it gives Dr. Collery the chance to explore how the eye could potentially repair itself, offering a glimpse into the future of therapies for vision restoration.
The fish also reproduce quickly, with hundreds of offspring born each week, making them an ideal system for testing multiple genetic changes at once, or for screening therapeutic drug libraries. With this rapid reproduction, Dr. Collery can analyze how different genetic mutations affect the fish’s vision, leading to new insights about human eye diseases.
Editing Genes to Unlock New Possibilities
One of the most exciting aspects of Dr. Collery’s research is his use of CRISPR technology, which allows him to edit genes with incredible precision. With this powerful tool, he can make specific changes to the zebrafish’s DNA and study how those changes impact vision. Routinely, his team inactivates genes linked to human blinding diseases to see if zebrafish also lose their eyesight, to see if the same process affects both species.
One of the key proteins he’s studying is STRA6, a retinoid transporter that plays a critical role in delivering vitamin A to photoreceptors—the cells in the eye that allow us to see. By knocking out the STRA6 gene in zebrafish using CRISPR, Dr. Collery can study what happens when the eye doesn’t get the nutrients it needs, providing valuable insights into how genetic mutations cause vision loss and whether there are ways to reverse these effects.
“When that protein [STRA6] is absent, the eye is no longer able to import the retinoids,” Dr. Collery says. “The retinal pigment epithelium (RPE) was very unhappy, it took on a very aberrant appearance. The photoreceptors also were very unhappy when they were being deprived of the nutrient they need for ongoing activity.”
This disruption in nutrient supply has profound effects on both the RPE, which supports photoreceptors, and the photoreceptors themselves, ultimately contributing to vision loss. Emerging work suggests that this loss of vitamin A may also affect genetic signaling in the eye, another exciting avenue to explore and understand.
The Path to Potential Treatments
Dr. Collery ultimately aims to develop therapies that could help people suffering from retinal diseases or refractive errors. With the zebrafish model as his starting point, he’s testing different treatments to see if they can restore damaged retinal cells.
For instance, he’s investigating whether delivering vitamin A analogs to the fish can help their photoreceptors recover. He’s seen signs that the zebrafish photoreceptors can regenerate when they’re given the right nutrients, something that’s typically not possible in humans.
Dr. Collery is also exploring the possibility of gene therapy—delivering healthy copies of genes to replace defective ones.
“One of the best treatments that I can think of currently would be a gene therapy approach. You could inject into human eyes and literally redeliver or restore the missing gene that people might have that is causing a disease phenotype,” he says.
The results of Dr. Collery’s research could be a game-changer for people living with retinal diseases. With a recent grant, he’s delving deeper into understanding how retinoid signaling works in the eye, not just in development, but in maintaining eye health over the long term.
By identifying key pathways involved in eye homeostasis, he hopes to uncover new ways to prevent or treat degenerative eye diseases. As his work progresses, it brings new hope for better treatments and potential cures for retinal degeneration and refractive errors.
“If we can understand how the zebrafish regenerates or repairs its cells, we could potentially develop therapies that would restore vision in humans,” Dr. Collery says.
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