A niche for the eye

Date:
January 13, 2021
Source:
Stowers Institute for Medical Research
Summary:
What if the degenerative eye conditions that lead to glaucoma,
corneal dystrophy, and cataracts could be detected and treated
before vision is impaired? Recent findings point to the ciliary
body as a key to unlocking this possibility.



FULL STORY ==========================================================================
What if the degenerative eye conditions that lead to glaucoma, corneal dystrophy, and cataracts could be detected and treated before vision is impaired? Recent findings from the lab of Investigator Ting Xie, PhD,
at the Stowers Institute for Medical Research point to the ciliary body
as a key to unlocking this possibility.


========================================================================== Previous work from the lab showed that when mouse stem cells were differentiated into light-sensing photoreceptor cells in vitro, and
then transplanted back into mice with a degenerative condition of the
retina, they could partially restore vision. However, the transplanted photoreceptors only lasted three to four months.

"You cannot cure the condition in a diseased eye if you don't know what
causes the disease," says Xie. "This has been a major hurdle for stem
cell therapy in treating degenerative diseases." To this end, Xie's
group began to study the eye tissue microenvironment, specifically a specialized tissue in the eye called the ciliary body. Located at the
posterior edge of the iris, it is known to maintain ocular pressure
by secreting aqueous humor, the clear fluid between the lens and the
cornea. It has a similar function in mice and in humans, and defects in
the ciliary body manifest in similar ways in the mouse and human eye.

"People think the ciliary body is boring," says Xie. This might be because
the ciliary body was once thought to have a reserve of retinal stem cells,
Xie explains, which turned out not to be true. However, its role in eye
biology turns out to be quite broad, and "without a functioning ciliary
body, the eye degenerates," Xie adds.

When the Notch signaling pathway -- an important cell signaling
system found across the animal kingdom -- is defective in the ciliary
bodies of newly born mice, they fail to develop folds, and secretions
decrease, leading to shrunken vitreous bodies. In adult mice, defects
in Notch signaling cause low eye pressure, a shrunken vitreous, and
eye degeneration. Inactivation of the downstream transcription factor
RBPJ in the ciliary body also leads to the same effects. Before now,
the underlying molecular 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 wherein Notch and Nectin proteins in the ciliary body function in the development and maintenance
of eye tissue and structure.

In this report, the researchers describe the roles of adhesion protein
Nectin1 and gap junction protein Connexin43 in the ciliary body of
mice. They found that Notch2/3-Rbpj signaling in the outer ciliary
epithelium controls the expression of Nectin1, which works with Nectin3
in the inner ciliary epithelium to keep the two tissue layers together,
which promotes proper folding of the ciliary body. They found that
Notch signaling also maintains the expression of Connexin43 in the outer ciliary epithelium, while Nectin1 localizes and stabilizes Connexin43 on
the lateral surface, which maintains the vitreous body and intraocular pressure.

Lastly, the researchers found that in addition to maintaining ocular
pressure and directing ciliary body morphogenesis, 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 nutritive support for the cornea, the lens, and the retina.

"We propose the ciliary body could be a niche for the eye tissues,"
explains Xie, in the sense that it can behave like a stem cell niche, by providing signals that affect cellular morphogenesis and function. "The
next important question is what other protein factors secreted by the
ciliary body are important for maintaining the cornea, the lens, and
the retina, respectively.

Some of these factors could be involved directly in eye diseases."
This work was supported by the Stowers Institute for Medical Research,
the National Eye Institute of the National Institutes of Health (award R01EY027441 to TX), and a China National Scholarship (JP). The content
is solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health.


========================================================================== Story Source: Materials provided by
Stowers_Institute_for_Medical_Research. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. Ji Pang et al. NOTCH Signaling Controls Ciliary Body Morphogenesis
and
Secretion by Directly Regulating Nectin Protein Expression. Cell
Reports, 2021 DOI: 10.1016/j.celrep.2020.108603 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/01/210113132407.htm

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