In Terminator 2, Arnold Schwarzenegger's character wanted to know why humans cry. Future robots might get to experience it themselves, following the production of artificial glands that produce actual tears. The glands are based on those of mice, not humans, so we are still a way off from offering tear gland transplants to anyone who has lost the ability to cry, but their creation could help us understand dry-eye disease.
Aside from their engagement in our most emotional moments, tear glands are essential to keep the eye healthy, providing the film that lubricates and protects it from bacteria. Sjögren's syndrome, an autoimmune disease that reduces both tear and saliva production, is just one of the many causes of dry eyes that can be painful or even blinding. Existing treatment options include surgery and eye drops, but researchers at the Hubrecht Institute hope we can expand the choices if we understand the problem better, for which artificial tear glands could help.
"What struck us is that at least 5% of the adult population is estimated to have dry-eye disease, which is most of the time related to a defect of tear production by the tear gland," Dr Yorick Post said in a statement. "But treatment options are limited because there was no complete understanding of the biology and no reliable, long-term in vitro model to study the tear gland."
Prost and colleagues announced in a paper published in Cell Stem Cell they created organoids (3D structures that mimic some or all of an organ's functions) from both mouse and human stem cells. Gradually the mouse versions were expanded to replicate entire tear glands. When exposed to noradrenaline, a neurotransmitter that induces tears, they swelled up like balloons.
"We had to modify the cocktail of factors the organoids are grown in so that they would become the mature cells that we have in our tear glands and that are capable of crying," said co-first author PhD student Marie Bannier-Hélaouët. Once done, the glands were always wet, like healthy eyes.
Having achieved this goal the team set about exploring the genes that make tear glands work. They deleted PAX6, the master gene that controls the development of sensory organs, including eyes, from the mouse organoids and found the cells no longer differentiated properly. PAX6 deficiency has been suspected as a possible cause of Sjögren's syndrome, so the newly created model should allow researchers to test possible treatments.
The in vitro tear glands also revealed a difference in the chemistry of the liquids secreted by two types of cells within the glands. These blend together to give the tears we know, so no one had previously noticed the difference in living eyes, be they human or rodent.
The authors also managed to transplant human organoid cells into mouse glands, leading to protein-producing duct-like structures made of human cells. Ideally, this could be a step towards regenerating non-functioning tear ducts, but the authors warn this is a much more distant goal than the knowledge to be gained from the tear glands in the lab.
It's unlikely mouse tear glands will prove exceptionally popular outside of research purposes, but we can think of a lot of people who'd love to possess an on-demand source of crocodile tears.