Glaucoma can progress unnoticeably at night

Intraocular pressure changes throughout the day and in some people it increases at night. Now scientists from Kyushu University have figured out one of the possible mechanisms of this process.: norepinephrine, which affects the functioning of the cells of the drainage system of the eye through the RHOB molecule, can play a role. So far, the results have been obtained on human and mouse cells, but in the future they may help to more accurately monitor pressure changes and select treatments. About why glaucoma can remain unnoticeable during daytime examination and what happens to the eyes at night — in the material of Izvestia.

Eye pressure lives by its own clock

The study is published in the journal Communications Biology. Kyushu University scientists studied why intraocular pressure rises at night using human and mouse trabecular meshwork cells, as well as animal experiments. It is the trabecular meshwork that is responsible for a significant part of the outflow of fluid from the eye and at the same time helps to clear the drainage pathway of small particles and waste.

This is especially important for glaucoma, as routine examinations are more often performed during the daytime. If the pressure is lower during this period, the changes that occur at night may potentially go unnoticed. However, scientists do not claim that a nighttime increase in blood pressure alone means the presence of glaucoma: the disease is associated with damage to the optic nerve, and intraocular pressure is one of the risk factors.

Eye drainage works differently at night

To understand the mechanism of increased blood pressure at night, the researchers turned their attention to norepinephrine, a neurotransmitter released by the sympathetic nervous system. They exposed human and mouse trabecular meshwork cells to this substance and compared changes in their activity. As a result, the scientists found 18 genes whose activity increased in both models, and focused on one of them, RHOB.

The RHOB molecule is involved in regulating the shape and movement of cells, as well as intracellular transport. Experiments have shown that norepinephrine increased its level in the cells of the trabecular meshwork. When RHOB was removed from human cells, they were better able to capture and remove particles. On the contrary, increasing RHOB levels reduced this cleansing activity and fluid movement.

Thus, scientists suggest the following chain: at night, the activity of the sympathetic nervous system leads to the release of norepinephrine, which increases the level of RHOB, and changes in the work of the cells of the trabecular meshwork impair the purification and outflow of fluid. As a result, intraocular pressure increases. This mechanism, according to the authors, may explain one of the causes of nocturnal pressure fluctuations.

A new target for treatment

The next step was to check whether it was possible to influence the discovered mechanism. In experiments on mice, they used eye drops that inhibit the chemical pathway RHO–ROCK, which regulates the activity of RHOB. After applying the drops, the nocturnal increase in intraocular pressure decreased.

The researchers consider the RHOB pathway as a potential target for future methods of controlling nocturnal pressure build-up. At the same time, we are not talking about a ready-made treatment yet: the results of experiments on mice cannot be directly transferred to humans, and the effectiveness and safety of this approach have yet to be studied. In addition, drugs that affect ROCK are already used in the treatment of glaucoma, but scientists need to find out separately whether the time of their use can affect the circadian rhythm of intraocular pressure.

The work also draws attention to a broader issue — the role of circadian rhythms in eye health. The researchers note that intraocular pressure is regulated by the internal biological clock, and circadian rhythm disorders may be associated with an increased risk of glaucoma. This may be especially important for the elderly, whose internal biological clock is more often out of sync.

The authors hope that understanding the nocturnal mechanism of pressure increase will help improve the early detection of glaucoma and create treatment regimens that take into account the time of day. However, so far the results of the study are fundamental: scientists have discovered a potential mechanism and a possible therapeutic target, but have not proposed a new diagnostic or treatment method for patients.