Impacts of sulfate polysaccharide JCS1S2 on retinal neovascularization in oxygen-induced retinopathy rat

Yang Bai ¹ Can Jin ² Rui Wang ¹ Lili Wang ¹ Yun Tang ¹ Han Wang ¹ Kan Ding ^2* Shanjun Cai ^1*

• ¹ Zunyi Medical University, Zunyi, China
• ² Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Zhongshan, China

Retinal neovascularization, a pathological form of angiogenesis, is a leading cause of blindness. Dendrobium sulfate polysaccharide JCS1S2, derived from Dendrobium chrysogenum, was the focus of this investigation into its effects on oxygen-induced retinopathy (OIR) in rat models and the Müller cells of the rat retina. To this end, we established an OIR rat model and divided the rats into three primary groups: Group I (control), Group II (OIR), and Group III (OIR + JCS1S2). Group III was further subdivided into three subgroups treated with different concentrations of JCS1S2 (10 μg/μL, 20 μg/μL, and 40 μg/μL). ADP and HE staining revealed that JCS1S2 dose-dependently inhibited retinal neovascularization. Quantitative PCR and Western blot analyses showed significant down-regulation of VEGF-A, VEGF-B, VEGF-D, VEGF-R1, and VEGF-R2 following JCS1S2 treatment. Transcriptome analysis suggested that JCS1S2 may suppress the activation of the TOLL-like receptor signaling pathway, regulate the expression of genes associated with endothelial activation and angiogenesis, and participate in the inflammatory and metabolic pathways of the retina. Western blotting data indicate that JCS1S2 can markedly reduce abnormal retinal angiogenesis and Müller cell activation in OIR rats through the TLR4/p-NF-κB/VEGF pathway, suggesting its potential as a therapeutic agent for retinal neovascularization.