Sagittaria Sagittifolia Polysaccharide Ameliorates Diabetic Retinopathy in Mice via Inhibiting TLR4-Mediated Microglial Activation.

Sagittaria sagittifolia polysaccharide (SSP) exhibits anti-inflammatory, antioxidant, lipid-regulating, and hypoglycemic properties, demonstrating therapeutic potential against diabetic retinopathy (DR). This study aimed to investigate the intervention efficacy of SSP in DR mice and its regulatory effects on retinal microglia activation. The type 2 diabetic mouse model was established by high-fat diet feeding combined with streptozotocin (STZ) intravenous injection. At week 9, retinal vascular pathology was assessed via fundus photography and fluorescein angiography. Serum lipid metabolism TG, CHO, LDL, and HDL were quantified using an automated biochemical analyzer. Retinal histopathology and thickness were evaluated through HE staining combined with Evans blue staining. Microglial activation adjacent to retinal vasculature was visualized by immunofluorescence, while retinal apoptosis was examined using immunohistochemistry and TUNEL staining. Co-localization of TLR4 and Iba was analyzed by immunofluorescence. Protein expression levels of TLR4, Myd88, P-p65, and total p65 in retinal tissues were determined by Western blot. SSP treatment significantly attenuated DR progression, as evidenced by preserved retinal vascular integrity, restored retinal thickness, reduced vascular leakage, lowered fasting blood glucose, and regulated lipid metabolism (reduced TG/TC/LDL-C, increased HDL-C). Furthermore, SSP suppressed pathological recruitment of microglia to retinal vasculature and inhibited their pro-inflammatory morphological transition. Mechanistically, SSP downregulated TLR4/Iba co-expression and inhibited the downstream Myd88/NF-κB signaling pathway. The study results demonstrated that SSP can delay the progression of retinopathy in type 2 diabetic mice. This mechanism seems to be associated with SSP's hypoglycemic and lipid-regulating effects, along with its inhibition of microglia-mediated inflammatory responses.