Tears from a test tube
The lacrimal gland secretes the liquid part of the tear film and is necessary for lubrication and protection of the eye. Dysfunction of tear production or secretion can lead to dry eye syndrome, as well as Sjogren's syndrome, a poorly understood autoimmune disease that causes dry eyes and mouth. Currently, treatment options for patients with lacrimal gland diseases include eye drops, clogging of tear points and surgical intervention.
a is the lacrimal gland of the right eye, b is the upper lacrimal point, c is the upper lacrimal canal, d is the lacrimal sac, e is the lower lacrimal point, f is the lower lacrimal canal, g is the nasolacrimal duct. Erin_Silversmith, Wikimedia.
According to various estimates, at least 5% of the adult population suffers from dry eye syndrome. At the same time, treatment options are limited by the lack of a complete understanding of the work of the lacrimal gland and a qualitative in vitro model for its study.
A group of researchers from the Huebrecht Institute, the Netherlands, created three-dimensional organoids of mouse and human lacrimal glands derived from adult stem cells, adapting a protocol they had previously used for other organs. Organoids can increase over several months and reproduce the structural, transcriptional and functional features of the epithelium of the lacrimal gland – the tissue that secretes most of the lacrimal fluid. It is noteworthy that the organoids increased in size after exposure to the neurotransmitter norepinephrine, which triggers the secretion of tears.
The task was to make the organoids "cry", since this is a sign of the lacrimal gland. The researchers had to change the combination of factors in which organoids are grown in order to achieve this goal.
They used mouse organoids to study the role of the Pax6 gene, the main regulator of eye development. Using the CRISPR/Cas9 genome editing technique, the researchers removed Pax6 and found that this gene makes an important contribution to the maturation of adult lacrimal gland epithelial cells. These data can provide valuable information for the creation of potential treatments for Sjogren's syndrome, since PAX6 deficiency is observed in the eye tissues of patients.
Using single-cell mRNA sequencing, the researchers also studied the cellular features and origin of tear components in the lacrimal gland. They demonstrated that ductal and acinar cells of the human lacrimal gland secrete different components of tears.
To test the potential of organoids for regenerative medicine, the researchers transplanted human organoids into the lacrimal glands of a mouse. Two weeks later, the transplanted cells formed ductal structures that remained in the lacrimal gland for at least two months. It turned out that the grafted organoids self-organize, and some cells proliferate within two months after transplantation. Moreover, the researchers found tear proteins inside the ducts formed by the transplanted cells.
Good results of organoid transplantation will need to be confirmed in mouse models of dry eye syndrome. Future research may also focus on modeling Sjogren's syndrome by incorporating immune cells into organoids. In addition, lacrimal gland organoids can be used as a model for testing new drugs and individual study of lacrimal gland diseases.
Article by M.Bannier-Hélaouët et al. Exploring the human lacrimal gland using organoids and single-cell sequencing is published in the journal Cell Stem Cell.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the Hubrecht Institute: Crying human tear glands grown in the lab.