Tetrahydrobiopterin (BH4) is a cofactor for aromatic amino acid hydroxylases and an essential cofactor for nitric oxide synthase (NOS), which is used in the study of endothelial dysfunction such as hypertension, hypercholesterolemia, and diabetes.

Microglia cultures under hyperoxic conditions were supplemented with or without Tetrahydrobiopterin (100 μM). Exposure of microglia to hyperoxia-induced oxidative stress for 24 h showed a significant increase in TSP-1 mRNA expression and protein compared with normoxia (21% O2). Tetrahydrobiopterin supplementation significantly prevents hyperoxia-induced microglial activation and prevents microvascular damage in choroidal explants by reducing Iba-1 and TSP-1 expression.[1]

To assess the levels of tetrahydrobiopterin in the retina, three to five retinal pools were collected from WT and HPH-1 mice at postnatal ages 7, 14, and 22 years and evaluated by LC-MS/MS. LC-MS/MS analysis confirmed that the concentration level of tetrahydrobiopterin in the retinal tissue of HPH-1 mice was significantly reduced by approximately 90% compared with WT groups P7, P14, and P22, respectively.[1]