aqueous humor

# Melatonin and the Eye: Nighttime IOP and Neuroprotection **Melatonin** is a neurohormone produced in a ~24-hour cycle (circadian rhythm) that plays key roles in sleep regulation and acts as a powerful antioxidant. In the eye, melatonin is synthesized locally (in the retina and ciliary body) and binds to **MT1/MT2 melatonin receptors** on ocular cells ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC12108883/#:~:text=Circadian%20variation%20in%20melatonin%20concentration,%E2%80%94a%20regulatory%20link%20between)). Its levels peak at night, coinciding with the normal drop in blood pressure and (in healthy individuals) the typical reduction in intraocular pressure (IOP) during sleep. These circadian patterns mean melatonin helps modulate **aqueous humor** (the watery fluid filling the front of the eye) dynamics. In turn, this affects nighttime IOP and retinal health, especially in aging. Recent studies suggest that impaired melatonin signaling may contribute to glaucoma risk, while melatonin analogs (drugs that mimic melatonin) show promise in lowering IOP and protecting retinal neurons ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC12108883/#:~:text=Circadian%20variation%20in%20melatonin%20concentration,%E2%80%94a%20regulatory%20link%20between)) ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC12108883/#:~:text=Apart%20from%20MT3%20activation%2C%20MT2,examined%20the%20effects%20of)). ## Ocular Melatonin and Circadian Control Melatonin is not only made by the pineal gland but also produced in the eye itself. Photoreceptors in the retina generate melatonin at night, and the ciliary body (the gland that produces aqueous humor) also synthesizes melatonin and releases it into the aqueous ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC12108883/#:~:text=Circadian%20variation%20in%20melatonin%20concentration,%E2%80%94a%20regulatory%20link%20between)) ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC12108883/#:~:text=circadian%20rhythm%20disturbances%20observed%20in,27%20%2C%2034%2C29)). This means melatonin levels in the **aqueous humor** rise in darkness, peaking around midnight to 2–4 AM ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC12108883/#:~:text=Circadian%20variation%20in%20melatonin%20concentration,%E2%80%94a%20regulatory%20link%20between)). By contrast, light exposure (especially blue light) suppresses melatonin via melanopsin-containing retinal ganglion cells. Thus, melatonin is a bridge between circadian signals (day–night) and intraocular physiology. Receptors for melatonin (MT1, MT2 and possibly MT3) are found on cells of the eye, including the **non-pigmented ciliary epithelial cells** that secrete aqueous humor ([pmc.ncbi.nlm.nih.gov](https://pmc.ncbi.nlm.nih.gov/articles/PMC12108883/#:~:text=Circadian%20variation%20in%20melatonin%20concentration,%E2%80%94a%20regulatory%20link%20between)). Activation of these receptors infl

Melatonin, Circadian Rhythms, and Nocturnal IOP Dynamics

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