Human eyes are complex and irreparable, yet they are structurally like those of the freshwater apple snail, which can completely regenerate its eyes. Alice Accorsi , assistant professor of molecular and cellular biology at the University of California, Davis, studies how these snails regrow their eyes — with the goal of eventually helping to restore vision in people with eye injuries.
In a new study published Aug. 6 in Nature Communications , Accorsi shows that apple snail and human eyes share many anatomical and genetic features.
"Apple snails are an extraordinary organism," said Accorsi. "They provide a unique opportunity to study regeneration of complex sensory organs. Before this, we were missing a system for studying full eye regeneration."
Her team also developed methods for editing the apple snail's genome, which will allow them to explore the genetic and molecular mechanisms behind eye regeneration.
A not-so-snail's paced snail
The golden apple snail (Pomacea canaliculata) is a freshwater snail species from South America. It's now invasive in many places throughout the rest of the world, but Accorsi said the same traits that make apple snails so invasive also make them a good animal to work with in the lab.
"Apple snails are resilient, their generation time is very short, and they have a lot of babies," she said.
In addition to being easy to grow in the lab, apple snails have "camera-type" eyes — the same type as humans.
Snails have been known for their regenerative abilities for centuries — in 1766, a researcher noted that decapitated garden snails can regrow their entire heads. However, Accorsi is the first to leverage this feature in regenerative research.
"When I started reading about this, I was asking myself, why isn't anybody already using snails to study regeneration?" said Accorsi. "I think it's because we just hadn't found the perfect snail to study, until now. A lot of other snails are difficult or very slow to breed in the lab, and many species also go through metamorphosis, which presents an extra challenge."
Eyes like a camera
There are many types of eyes in the animal kingdom, but camera-types eyes are known for producing particularly high-resolution images. They consist of a protective cornea, a lens for focusing light and a retina that contains millions of light-detecting photoreceptor cells. They are found in all vertebrates, some spiders, squid and octopi, and some snails.
Using a combination of dissections, microscopy and genomic analysis, Accorsi's team showed that the apple snail's eyes are anatomically and genetically similar to human eyes.
"We did a lot of work to show that many genes that participate in human eye development are also present in the snail," Accorsi said. "After regeneration, the morphology and gene expression of the new eye is pretty much identical to the original one."
How to regrow an eye
So, how do the snails regrow their eyes after amputation? The researchers showed that the process takes about a month and consists of several phases. First, the wound must heal to prevent infection and fluid loss, which usually takes around 24 hours. Then, unspecialized cells migrate and proliferate in the area. Over the course of about a week and a half, these cells specialize and begin to form eye structures including the lens and retina. By day 15 post-amputation, all of the eye's structures are present, including the optic nerve, but these structures continue to mature and grow for several more weeks.
"We still don't have conclusive evidence that they can see images, but anatomically, they have all the components that are needed to form an image," said Accorsi. "It would be very interesting to develop a behavioral assay to show that the snails can process stimuli using their new eyes in the same way as they were doing with their original eyes. That's something we're working on."
The team also investigated which genes were active during the regeneration process. They showed that immediately after amputation, the snails had about 9,000 genes that were expressed at different rates compared to normal adult snail eyes. After 28 days, 1,175 genes were still expressed differently in the regenerated eye, which suggests that although the eyes look fully developed after a month, complete maturation might take longer.
Genes for regeneration
To better understand how genes regulate regeneration, Accorsi developed methods to edit the snails' genome using CRISPR-Cas9.
"The idea is that we mutate specific genes and then see what effect it has on the animal, which can help us understand the function of different parts of the genome," said Accorsi.
As a first test, the team used CRISPR/Cas9 to mutate a gene called pax6 in snail embryos. Pax6 is known to control the development and organization of brain and eye in humans, mice and fruit flies. Like humans, snails have two copies of each gene – one from each parent. The researchers showed that when apple snails have two non-functional versions of pax6, they develop without eyes, which shows that pax6 is also essential for initial eye development in apple snails.
Accorsi is working on the next step: testing whether pax6 also plays a role in eye regeneration. To determine this, researchers will need to mutate or turn off pax6 in adult snails and then test their regenerative ability.
She is also investigating other eye-related genes, including genes that encode specific parts of the eye, like the lens or retina, and genes that control pax6.
"If we find a set of genes that are important for eye regeneration, and these genes are also present in vertebrates, in theory we could activate them to enable eye regeneration in humans," said Accorsi.
Additional authors on the study are Asmita Gattamraju of UC Davis, and Brenda Pardo, Eric Ross, Timothy J. Corbin, Melainia McClain, Kyle Weaver, Kym Delventhal, Jason A. Morrison, Mary Cathleen McKinney, Sean A. McKinney and Alejandro Sanchez Alvarado of the Stowers Institute for Medical Research. Accorsi performed most of the research for this study at Stowers Institute for Medical Research, where she worked as a postdoctoral fellow before joining UC Davis in 2024.
The study was funded by the Howard Hughes Medical Institute, the Society for Developmental Biology, the American Association for Anatomy and the Stowers Institute for Medical Research.
