Is Glaucoma an Autoimmune Condition?
The consensus on the progressive blindness of glaucoma is that the primary cause is rising pressure in the eye, resulting from an age-related failure of fluid flow in surrounding structures. Medications that reduce pressure in the eye, such as by reducing the pace of creation of new fluid, slows down the loss of sight associated with glaucoma, but even after successful treatment the condition can still progresses towards blindness. Researchers may now have identified why this is the case, and here present evidence to suggest that a form of autoimmunity is the process that causes loss of vision.
One of the biggest risk factors for glaucoma is elevated pressure in the eye, which often occurs as people age and the ducts that allow fluid to drain from the eye become blocked. The disease often goes undetected at first; patients may not realize they have the disease until half of their retinal ganglion cells have been lost. Most treatments focus on lowering pressure in the eye (also known as intraocular pressure). However, in many patients, the disease worsens even after intraocular pressure returns to normal.
"That led us to the thought that this pressure change must be triggering something progressive, and the first thing that came to mind is that it has to be an immune response." To test that hypothesis, the researchers looked for immune cells in the retinas of mice exhibiting glaucoma and found that indeed, T cells were there. This is unusual because T cells are normally blocked from entering the retina, by a tight layer of cells called the blood-retina barrier, to suppress inflammation of the eye. The researchers found that when intraocular pressure goes up, T cells are somehow able to get through this barrier and into the retina.
The researchers generated high intraocular pressure in mice that lack T cells and found that while this pressure induced only a small amount of damage to the retina, the disease did not progress any further after eye pressure returned to normal. Further studies revealed that the glaucoma-linked T cells target proteins called heat shock proteins, which help cells respond to stress or injury. Normally, T cells should not target proteins produced by the host, but the researchers suspected that these T cells had been previously exposed to bacterial heat shock proteins.
The researchers then turned to human patients with glaucoma and found that these patients had five times the normal level of T cells specific to heat shock proteins, suggesting that the same phenomenon may also contribute to the disease in humans. The researchers' studies thus far suggest that the effect is not specific to a particular strain of bacteria; rather, exposure to a combination of bacteria can generate T cells that target heat shock proteins.
Very interesting. I wouldn't be surprised if the next study discovers a high contribution from the senescent cells , and by extension, could be a good target for senolitic therapies.
Really interesting paper on potential metabolite biomarkers in senescent cells (open access):
"The induction of the fibroblast extracellular senescence metabolome is a dynamic process"
the paper moves beyond p16 to investigate different factors
Glaucoma is a target of senolytic treatments: