Hydroxytyrosol-Rich Olive Mill Wastewater, a Potential Protector Against Dyslipidemia, Diabetes, and Diabetic Retinopathy in Psammomys obesus

Olive mill wastewater (OMWW), a byproduct of olive oil extraction, constitutes a natural resource of phenolic compounds. Hydroxytyrosol (HT), the predominant compound, was reported to have antioxidant, anti-inflammatory, and neuroprotective effects. This research aims to evaluate the effect of OMWW bioproduct rich in HT on retinal glial function, glutamate metabolism, and synaptic transmission alterations mediated by hyperglycemia and dyslipidemia in high-calorie diet (HCD)-induced diabetic retinopathy (DR) in Psammomys obesus. Animals were divided into four groups. Two diabetic animal groups (D) received an HCD, one untreated (D) and another receiving HT-OMWW treatment (20 mg/kg body weight: bw) (D+); the two other groups were used as controls (C and C+). During 7 months, food and water intake, body weight, glycemia, hematocrit, and serum lipid parameters were assessed. At 3, 5, and advanced 7 months of DR, immunohistochemical studies were performed to identify key proteins implicated in the protection of DR. HT-OMWW has anti-obesity, hypoglycemic, and hypolipidemic effects. Its long-term administration attenuates retinal glial reactivity, microglia number, changes in glutamate homeostasis, and synaptic function in diabetic animals with retinopathy. These results suggest that HT-OMWW extract seems to have promising in vivo anti-diabetic, anti-dyslipidemic, and neuroprotective effects in P. obesus, a model of DR-like humans.