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Comment by colechristensen | Hacker News Reader

I have read papers for similar genetic engineering in eyes. They infect the eye (or specific retina areas) with a virus, there is local inflammation while the immune system does its job with some mild side effects for a few weeks at most.

After the viral infection i never saw any mention of immune rejection or other reaction to the modified tissues.

From my limited understanding, in order to have an immune response there has to be something different for the immune system to “see” usually on the surface of cells... expressing a protein inside apparently doesnt raise to that level.

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Caveat: I did not read the paper but can weigh in on this:

1. The eye has immune privilege, similar to that of the brain, meaning it can tolerate antigens that would normally trigger an immune response elsewhere, like your arm.

2. Fragments of proteins expressed internally are normally presented on the surface of cells through a process called antigen-presentation. This allows immune cells to "see" when cells are infected and expressing proteins in the cytosol they normally would not.

Together this means that exogenous expression of proteins in the eye do not trigger inflammation because the eye is immune privileged, but if those proteins were expressed in the arm, there would be an immune response even if proteins are only cytosolic.

>1. The eye has immune privilege, similar to that of the brain, meaning it can tolerate antigens that would normally trigger an immune response elsewhere, like your arm.

This is my theory, too. I worked on optogenetics in the periphery and the immune response is catastrophic, often leading to loss-of-function worse than a pre-existing condition or trauma. The way we got around this was with immune response suppressants like Tacrolimus. [0]

But my expertise dramatically drops off with CNS immunity, not to mention the eyes which I know very little about.

[0] https://www.nature.com/articles/s41598-018-32075-0

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