Complement proteins C3 and C4: systemic innate immunity and glaucoma progression

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Complement proteins C3 and C4: systemic innate immunity and glaucoma progressionGlaucoma is a chronic eye condition in which the optic nerve slowly deteriorates, leading to progressive vision loss (). While high eye pressure is a well-known risk factor, emerging research suggests the immune system – especially the innate immune system – may also influence glaucoma. In particular, scientists are studying complement proteins C3 and C4, which are blood proteins involved in the body’s first-line defense, to see if they play a role in optic nerve damage. This article explains what C3 and C4 do, how complement activation might relate to glaucoma damage, and whether measuring C3/C4 in the blood could help predict disease progression (compared with other inflammation tests like hs-CRP or the systemic immune-inflammation index (SII)). We will also note factors (like autoimmune disease or infection) that can affect complement levels, and mention any known genetic links. The complement system and innate immunityThe complement system is part of innate immunity – the body’s rapid, non-specific defense against infections or damage. Complement consists of a cascade of proteins in the blood that, when activated, help “tag” invading microbes or dying cells so they can be cleared by immune cells. A key step in all complement pathways is the activation of C3, a protein that splits into fragments that mark targets for destruction. The classical pathway (triggered by antibodies) and lectin pathway both use C4 early on, while the alternative pathway can amplify C3 directly. When complement is active, it helps drive inflammation and cell cleanup. For example, doctors often measure C-reactive protein (CRP) – another inflammation-related protein – to see if patients have systemic inflammation (). In a similar way, unusually high or low levels of complement proteins can indicate immune activation or consumption. Blood tests for C3 and C4 are widely available through medical labs. These tests report a patient’s C3 and C4 levels (usually in milligrams per deciliter) alongside reference ranges. Under normal conditions, C3 and C4 stay within a standard range. If a test shows low C3/C4, it can mean that complement is being actively used up (for example, in an ongoing autoimmune reaction). If levels are high, it may indicate an acute reaction to infection or injury. In practice, C3/C4 tests are commonly ordered by doctors for autoimmune diseases (like lupus) or certain infections. Patients can obtain these tests through their doctor, or in some regions via direct-to-consumer lab services. The results usually note “high,” “normal,” or “low” relative to normal ranges. For example, CRP (measured by a simple blood test) “can tell doctors how much inflammation” a patient has (), and doctors interpret complement similarly – in context. Because many conditions can affect complement levels, any abnormal result needs professional interpretation.Complement activation and glaucoma damageCould complement be involved in glaucoma neurodegeneration? In other words, does stress on the optic nerve trigger the complement cascade, contributing to damage? This is an area of active research. In many neurodegenerative diseases (such a