New Chinese research suggests that immune cells that migrate from the digestive tract to the eyes may be to blame for the inexplicable progression of vision loss in certain glaucoma patients despite treatment.
These “gut-retina axis” cells bind a certain protein to gain entry to the retinal ganglion cells (RGCs) of the eye, where they cause harm.
Glaucoma is a general name for eye conditions brought on by the loss of RGCs, whose axons make up the optic nerve that carries visual information to the brain. Glaucoma is categorized as a group of neurodegenerative disorders.
If you’re reading this with your eyes, your optic nerve is sending this information to your visual cortex in your brain for processing right now.
Glaucoma is a primary cause of blindness and is currently incurable; treatment seeks to slow the spread of the condition.
In their publication, the researchers state that their findings “emphasize the importance of the gut-retina axis in glaucoma pathogenesis and for the development of therapeutic strategies.”
The primary risk factor for glaucoma is increased intraocular pressure (EIOP), or pressure inside the eyeball. While lowering EIOP is one of the main therapy objectives, disease development isn’t always halted by doing so.
Prior research suggested that immune system T cells might contribute to glaucoma damage, but the fundamental mechanism remained a mystery.
According to the research team, which was led by clinical immunologists Chong He, Wenbo Xiu, Qinyuan Chen, and Kun Peng from the University of Electronic Science and Technology, “T cells and other circulating immune cells are normally denied permission to enter the retina.”
The four researchers participated in a 2021 study that discovered a subpopulation of CD4+ T cells express integrin 7, a gut-homing receptor that, with a little assistance from a protein known as mucosal addressin cell adhesion molecule 1 (MAdCAM-1), managed to enter the retina.
A connection between CD4+ T cells that express integrin 7, MAdCAM-1, and the severity of glaucoma disease in patients was validated by He, Xiu, and team in their most recent study.
Blood samples from 189 healthy controls and 519 glaucoma patients were tested first. In comparison to healthy controls, glaucoma patients had a much larger percentage of 7-expressing CD4+ T cells, and those who had more of these cells in their blood also had more severe eye injury.
The next step in the research involved demonstrating that 7+ CD4+ T cells in these early stage glaucoma mice must circumvent the gut in order to reach the retina. This was done by using an EIOP-induced mouse model of glaucoma.
The researchers discovered that the integrin 7+ CD4+ T cells of EIOP-induced mice were reprogrammed in the gut, allowing them to return to the blood circulation functionally prepared to travel to the retina.
Normal T cells are unable to bind to MAdCAM-1 in the retina, but gut-licensed T cells were able to do so, giving them access to the eye tissue, which “eventually led to neuroinflammation”.
The research claims that one of the mechanisms through which gut-licensed 7+ CD4+ T cells penetrate the blood-retina barrier and invade the retina is their capacity to stimulate MAdCAM-1 expression on retinal [vessels].
The team gave antibodies to mice that prevented the 7+ CD4+ T cells from interacting with MAdCAM-1 in order to study the relationship between these questionable cells and proteins and glaucoma damage. Glaucoma damage was considerably lessened by blocking communication with MAdCAM-1.
According to the authors’ research, gut-licensed 7+ CD4+ T lymphocytes and MAdCAM-1 play a part in the degeneration of retinal ganglion cells.
More study is required since it is unclear how EIOP raises blood levels of these 7+ CD4+ T cells and how they are reprogrammed in the gut.
The team says their work also illustrates the possible function of the immune system in disorders like glaucoma and draws the conclusion that clinical trials might investigate if the antibodies used in their study could treat glaucoma.
The study has been published in Science Translational Medicine.