What if the degenerative ocular conditions leading to glaucoma, corneal dystrophy, and cataracts could be detected and treated before vision was damaged? Recent results from the laboratory of Researcher Ting Xie, PhD, at the Stowers Institute for Medical Research identify the ciliary group as a key means of unraveling this potential.
Previous work from the laboratory showed, when mouse gas cells were differentiated into photoreceptor cells with light sensitivity in vitro, and then transmitted back to mice with degenerative condition of the retina, they were able to regain vision to some extent. However, the transplanted photoreceptors lasted only three or four months.
“You can’t cure the condition in an infected eye if you don’t know what is causing the disease,” Xie says. “This has been a major obstacle to stem cell therapy in the treatment of degenerative diseases.”
To this end, the Xie group began studying the microenvironment of eye strain, specifically a specific substance in the eye called the ciliary group. Located at the posterior edge of the magazine, it is known to maintain ocular pressure by emitting aqueous humor, the clear fluid between the lens and the cornea. It has the same type of action in mice and in humans, and deficiencies in the ciliary body appear in similar ways to the mouse and the human eye.
“People think the ciliary body is pierced,” Xie said. This may be because the ciliary body was once thought to have a reserve of retinal cells, Xie explains, which turned out to be untrue. However, his role in ocular biology seems to be very broad, and “without an active ciliary body, the eye will shrink,” Xie adds.
When the Notch signal pathway – an important cell signaling system found throughout the animal kingdom – is deficient in the ciliary bodies of newborn mice, they fail to develop a fold, and secretions fail. reduction, leading to shrunken vital bodies. In adult mice, deficiencies in Notch symptoms lead to low eye pressure, shrunken vitreous, and eye degeneration. Inactivation of the transcription factor downstream RBPJ in the ciliary body also leads to the same effects. Prior to this, the underlying mechanism for this outcome was unclear.
In a paper published in Cell reports on January 12, 2021, first author Ji Pang, a visiting PhD student from Shanghai Jiao Tong University, China, and others describe a signaling pathway where Notch and Nectin proteins in the ciliary body are work in developing and maintaining eye tension and structure.
In this report, the researchers describe the roles of Nectin1 adhesion proteins and Connexin43 gap junction proteins43 in the ciliary body of mice. They found that Notch2 / 3-Rbpj signals in the outer ciliary epithelium control the expression of Nectin1, which works with Nectin3 in the inner ciliary epithelium to hold the two thin layers together , which promotes proper folding of the ciliary body. They found that Notch signals also maintain Connexin43 sensation in the outer ciliary epithelium, while Nectin1 locally and stabilizes Connexin43 on the lateral surface, which maintains the vitreous body and intraocular pressure.
Finally, the researchers found that in addition to maintaining ocular pressure and regulating the morphogenesis of the ciliary body, Notch2 / 3-Rbpj signaling in the inner ciliary epithelium also regulates the secretion of various proteins. such as Opticin and collagens into the vitreous body, providing nutritional support to the cornea, lens, and retina.
“We suggest that the ciliary body may be a special place for the eyeballs,” Xie explains, in the sense that it can behave as a cell gas niche, by providing signals. which affects cell morphogenesis and function. “The next important question is what other protein factors are secreted by the ciliary body important for the maintenance of the cornea, lens, and retina, respectively. Some of these factors may be be directly involved in eye diseases. “
This work was supported by the Stowers Institute for Medical Research, the National Institute of Ophthalmology at the National Institutes of Health (award R01EY027441 to TX), and the China National Scholarship (JP). The content is the sole responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.