Saffron (Crocins) in Optic Neuroprotection: Translating Retinal Evidence to Glaucoma

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Saffron (Crocins) in Optic Neuroprotection: Translating Retinal Evidence to GlaucomaSaffron (the dried stigmas of Crocus sativus L.) is rich in carotenoid compounds, especially crocins (glycosides) and their aglycone crocetin. These bioactives have potent antioxidant, anti-inflammatory and bioenergetic effects on retinal cells. In animal and cell models, saffron extracts and purified crocin/crocetin protect photoreceptors, retinal pigment epithelium (RPE), and retinal ganglion cells (RGCs) from oxidative injury () (). Clinically, most saffron trials have focused on age-related macular degeneration (AMD) and diabetic retinopathy, showing improved visual function with doses around 20–30 mg/day () (). Emerging data suggest these benefits might extend to glaucoma. In one small study of primary open-angle glaucoma (POAG), 30 mg/day saffron significantly lowered intraocular pressure (IOP) by ~3 mmHg without side effects (). Mechanistically, saffron’s anti-inflammatory and mitochondrial-support actions – such as dampening pro‐inflammatory cytokines and preserving cellular ATP – likely underlie these effects. Recent longevity research even shows crocetin can boost tissue energy metabolism and extend median lifespan in aged mice (). Below we review the preclinical evidence of saffron’s retinal neuroprotection and perfusion effects, discuss how these might apply to glaucoma (including potential impacts on RNFL thinning and visual fields), and cover dosing and safety considerations.Preclinical Evidence in Retinal ModelsAntioxidant neuroprotection. In vitro and animal studies consistently find that crocin and crocetin guard retinal cells against oxidative stress. For example, in vitro, crocin (0.1–1 µM) prevented H₂O₂-induced death of RGC-5 cells by lowering ROS, preserving mitochondrial membrane potential (ΔΨm) and activating NF-κB (). Crocin increased anti-apoptotic Bcl-2 and decreased pro-apoptotic Bax and cytochrome c, blocking the mitochondrial apoptosis cascade (). Likewise, in vitro crocetin protected cultured human RPE cells from tert-butyl hydroperoxide injury by preventing ATP loss, maintaining nuclear integrity, and triggering a rapid ERK1/2 survival signal (). In effect, crocetin preserved the cells’ energy production pathways (mitochondrial respiration and glycolysis) under oxidative stress (). These findings show saffron metabolites directly bolster the bioenergetic health of retinal cells.Animal studies echo these effects. In a rat model of retinal ischemia–reperfusion injury, crocin supplements reduced oxidative markers and caspase-3 levels, preserving retinal thickness (). In mice exposed to intense light (a photoreceptor “light damage” model), oral saffron or crocetin also prevented photoreceptor apoptosis and preserved visual responses () (). Moreover, saffron-fed animals showed less lipid peroxidation and higher antioxidant enzyme activity in the retina (), reflecting its free-radical scavenging. Notably, some studies suggest crocin boosts retinal blood flow after ischemia (), which could improve oxygen and nutrient delivery (though blood-flow data come mainly from animal models). Together, these data indicate that saffron’s neuroprotective effects in the retina involve both direct antioxidant action and preservation of mitochondrial ATP production () ().Anti-inflammatory effects. Chronic inflammation is implicated in glaucoma and other retinal diseases. In a mouse glaucoma model (laser-induced ocular hypertension), a saffron