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Is Immune System A Cause For Glaucoma?

Is Immune System A Cause For Glaucoma?

October 23, 2019

Before initiating the discussion about the relationship between the autoimmune disease and glaucoma, let’s have a quick review of the impact of the immune system on eyes. The body has various sites that are immune privileged. These sites are places in the body where the graft tissues can be placed without any concern of tissue rejection which when placed in non-privileged sites could have led to an inflammatory immune reaction. These sites have the ability to tolerate antigens without any immune response. Eyes along with anagen hair follicles, testicles, placenta and fetus, and central nervous system are considered as privilege organs for a long period. Various mechanisms are present in the eyes that prevent the action of the immune system in the eyes. First, the barrier system in eyes is so strong that it does not allow the entry of immune cells inside the eyes thereby preventing the immune response. Second, various immune cells, intrinsic to the ocular region are present, which detects the foreign antigen. These cells are responsible for suppressing the immune response of the systemic immune system. This suppression of the systemic immune system is known as the Anterior Chamber Associated Immune Deviation (ACAID).

Various studies have indicated the impact of the immune system on ocular health and the latest study has again concluded that autoimmune disease may have an impact on the development of glaucoma. However, the previous studies were having a little impact on the treatment of glaucoma and the treatment was mainly concentrated on reducing the intra-ocular pressure for the management of glaucoma.  The reason being not much of the information was available in context to the mechanism of autoimmune disease that may lead to glaucoma and lack of effective therapy for managing glaucoma due to autoimmune disease. It is also been indicated that in almost 25% of the people, increased intraocular pressure is not the cause for progressive glaucomatous neuropathy and the number of people in this class in Asia is even higher and is up to 90%. In such patients, direct stress on optic nerve and retina contributes to the symptoms of glaucoma. Various mechanisms are postulated for the development of glaucoma in these patients such as genetic mutation, underlying disease conditions such as ischemia, altered morphology of optic nerve and presence of aberrant immunity.

The study conducted at MIT and Massachusetts Eye and Ear has shown that autoimmunity may be one of the reasons behind the development of glaucoma. Scientists found that this mechanism may be true in patients whose glaucoma worsens even after maintaining the IOP at safer levels through medications. While finding the exact reason for this unusual condition, the reason that strikes the mind of scientists was the immune system. They were surprised to find that T cells were present in the retina of these mice because, in general conditions, these immune cells are blocked by the blood-retinal barrier to entry in the retina. The reason for this may be a change in permeability of the system due to increased ocular pressure due to which T cells find their way in the retina and continue to damage retina even when the IOP is normal.

It was also interesting to find that the mice with high intraocular pressure, which were devoid of T cells had no progression of disease after maintaining IPO at a safe level. The study also proposes the mechanism through which T cells damages the retina. The study reveals that the T cells target the heat shock protein that helps the retina to fight against stress. Normally, the immune system does not attack the protein of the host but due to earlier encounters by the bacterial heat shock protein, and due to a high level of similarity with the heat shock protein of mice, T cell attack the retinal T cell protein. This hypothesis was also tested by inducing glaucoma in mice who never encountered bacterial exposure. These mice were resistant to developing glaucoma.

The next question that needs to be answered was how far this study on mice applies to humans. The researchers of this study found that human with glaucoma has five times more T cells that target heat shock proteins. The researchers also pointed out that there is no specific bacterium that causes glaucoma and the mechanism is due to a combination of bacteria. This study will help in identifying potential tool for managing glaucoma by managing the autoimmune response. The researchers also believe that this mechanism may also apply to various neurological conditions related to autoimmune disease that may lead to advanced management of these conditions.


Nature Communications, 2018; 9 (1) DOI: 10.1038/s41467-018-05681-9

Exp Eye Res. 2011 Aug;93(2):187-90.


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