An old house stands because a repair crew lives in it. Spot a crack in the wall, patch it, paint it over, and the building takes a hit again. In the eye, that crew is a set of immune cells that gather around the drainage channel and keep pressure from climbing.
As we age, the channel that drains fluid from the eye narrows, like an aging pipe. In mice its area shrank from 1.299 to 1.118 ×10⁵ µm², and in people over 50 the channel is shorter than in younger ones. Yet pressure stays normal in most. Why? Because macrophages, the scavenger cells, pile up around the channel and release the protein VEGFA. This protein keeps the channel walls in working order, like a mason reinforcing old brickwork.
To find out who is in charge, the scientists deleted the Vegfa gene in mice, specifically in macrophages. Eye pressure jumped, and fluid outflow got worse. So the crew is not working for nothing. But there is a weak spot: the signal that calls it depends on the protein TIE2. When TIE2 is in short supply, the channel narrows more, macrophages become more numerous but fail to cope, and pressure rises even at a young age.
Glaucoma used to be seen as a purely mechanical problem: the pipe is clogged, so clear it. Now it is clear that a crew lives in the pipe, and whether vision holds out depends on its work. Boosting the TIE2 signal in older people might be possible without gene therapy, for instance with small molecules. Then, instead of daily drops, there would be long-term protection from blindness. The house ages, but the repair crew does not leave.
The area of Schlemm's canal in mice decreases with age by about 14%, comparable to the loss of aortic cross-sectional area in aging humans.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.