Senolytic against glaucoma
Drug from old cells prevented glaucoma in mice
Polina Loseva, N+1
Scientists have prevented the death of neurons in the retina of mice by ridding it of aged cells. To do this, they first used genetic methods of cell destruction, and then the well–known senolytic dasatinib. Senolytics, thus, theoretically can save from another disease – glaucoma. The work was published in the journal Aging Cell (Rocha et al., Early removal of senescent cells protects retinal ganglion cells loss in experimental ocular hypertension).
Over time, cells accumulate in the tissues of the body, which are called senescent, or old. They are not able to reproduce, but they are not in a hurry to die, but instead secrete a set of substances called SASP (senescence associated secretory phenotype, secretory phenotype associated with aging), which trigger tissue restructuring. But since the older the organism, the less resources it has for restructuring, most often the release of SASP ends with the destruction of tissue and the transformation of surrounding cells into senescent.
To prevent the "epidemic of aging", scientists have proposed selectively destroying senescent cells in tissues. At first, this was done by genetic methods, and then they began to use substances-senolytics. It is already known that senolytics can prolong the life of laboratory mice, but in order to use them on humans, it is necessary to find specific diseases against which they could be useful.
Senolytics have already been tested on models of a variety of diseases – from obesity to depression – and now Lorena Rocha from The University of California and her colleagues tried to use them against eye diseases. To do this, scientists artificially induced glaucoma in experimental mice: they were anesthetized, and then a saline solution was injected into the anterior chamber of the eye. At the same time, intraocular pressure increased, and it was maintained elevated for an hour. Under such pressure, scientists expected to detect the death of retinal cells in the eye.
Under the promoter of the p16 gene, a standard marker of senescent cells, a fluorescent gene was embedded in mice, as well as a gene for susceptibility to the drug ganciclovir. If such mice are treated with ganciclovir, then those cells in which p16 is active, that is, senescent, die.
After glaucoma was induced in the animals, the researchers divided the mice into two groups: one received ganciclovir, the other did not. Then, the number of ganglion neurons (these are cells that collect information from rods and cones) in the retina was counted in all of them. In mice that were given ganciclovir, they turned out to be on average about 75 percent of the norm, and in those who were not given about 50 percent. Finally, the amplitude of nerve impulses in the retina was measured in animals – in the group with ganciclovir, it turned out to be almost twice as high, which is necessary to preserve the activity of neurons. At the same time, senescent cells in the retina of these animals were found several times less than in the group that did not receive ganciclovir.
Then the researchers tried to reproduce the same experiment with the well-known senolytic dasatinib. It was administered intraperitoneally to transgenic mice after imitation of glaucoma. It turned out that dasatinib has the same effect on the retina as ganciclovir: the number of neurons did not differ in the control group and in the group with glaucoma, regardless of which senolytic they received.
Thus, scientists have confirmed that senolytics can be effective in another disease – glaucoma. Moreover, if they are applied immediately after exposure to the eye, they help prevent the death of nerve cells. This means, firstly, that senolytics can help in the prevention of glaucoma, which is usually detected already in the late stages of the disease, and secondly, that senolytics can be useful not only for the elderly, but also for young people.
Senolytics have two important drawbacks – selectivity of action and possible side effects. Therefore, scientists continue to look for new substances with senolytic properties. Recently, for example, it was proposed to use cardiac glycosides in this capacity. And dasatinib and quercetin, often used together with it, have already begun to be tested in small doses on patients with diabetes.
Portal "Eternal youth" http://vechnayamolodost.ru