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Immune System & Eye Disease: More than Meets the Eye

Posted by Ilena Di Toro | Posted on October 27, 2020

Having an immune system is a good thing. It deals with bacteria and viruses, so that either we don’t get sick or if we do, our body fights them off and, for the most part, sickness isn’t fatal. Sometimes our immune system doesn’t work the way we want it to. That can range from an allergic reaction to an autoimmune disease, like rheumatoid arthritis.

Of course, when it comes to the immune system and the eye, things aren’t always what they seem. Take retinitis pigmentosa. Many studies have shown that the complement system, which is part of the innate immune system, can make the disease worse. Yet, one study done at the National Eye Institute (NEI) showed that the complement system can either help or hurt, depending on context.

Scientists at NEI looked at the genetic expression of the complement system in a mouse model of retinitis pigmentosa. They found that complement expression coincided with the onset of photoreceptor degeneration and it occurred in the same place as the degeneration. They then looked at the role of C3, the central part of the complement and CR3, its receptor. Mice with genetically removed C3 and CR3 were compared with mice with normal expression of the pair. It was found that the absence of C3 and CR3 made degeneration worse.

In particular, the rod photoreceptors, the light sensing cells that go first when someone has retinitis pigmentosa, were lost in a wave of neurotoxic inflammatory cytokines. So, it is the breakdown of the C3 and CR3 interaction that leads to a decreased ability to dispose of dead photoreceptors, which then accumulate and lead to inflammation and degeneration. That means activation of the complement system helps to clear away dead cells and maintain homeostasis in the retina.

It isn’t always eye disease that can affect vision. Immunotherapy is used to treat cancers, such as cancer of the bladder, kidney and lung, which don’t respond to other forms of therapy. Yet, unlocking the power of the immune system does have its downside, namely it can lead to an attack on healthy organs, like the eye. Doctors at the University of Michigan Kellogg Eye Center had an article published in JAMA Ophthalmology that told of a case where three patients who were being treated with immune checkpoint inhibitors developed uveal effusions and eye inflammation that affected their vision.

These patients were receiving an anti-PD-1 or anti-PD-L1 antibody immune checkpoint inhibitor drug: atezolizumab, nivolumab or pembrolizumab and the effusions occurred within one to three months of receiving the inhibitors. The only way to stop the effusions was to stop using the immune inhibitors. So, the doctors asked the oncologists for each patient if the inhibitors can be discontinued. They were for two out of the three patients and the effusions improved within three months.

What lead to this reaction in the first place are high levels of the PD-L1 antibody in ocular tissue. Once the antibodies in the ocular tissue are compromised the effusions take place. That means as immunotherapy comes into greater use, researchers need to monitor side-effects and develop ways to minimize them.

These cases show the connections between eyes and the immune system can be complicated. When one genetic pathway is turned on or off, it can activate reactions that can lead to either sickness or health. All the more reason to be vigilant when it comes to eye health.


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