Aqueous humor levels of syndecan-1 and syndecan-4 associated with OCTA metrics in diabetic retinopathy

Jixian Ma¹Yue Bian¹Yazhou Qin¹Yuyao Qu¹Li Qin¹Anming Xie¹Qiuping Liu²Xiayu Xu³Jianqin Lei¹Jingming Li^1*

• ¹The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
• ²First Affiliated Hospital of University of South China, Hengyang, China
• ³Xi'an Jiaotong University School of Life Science and Technology, Xi'an, China

Purpose:In the study, we tested the associations between diabetic retinal vascular injuries, as evidenced by OCTA metrics, and levels of syndecan-1 and syndecan-4 in aqueous humor of diabetic patients. Methods:A prospectively designed cross-sectional study. The study enrolled 14 patients with DR, 8 patients with diabetes mellitus (DM) but no DR (NDR), and 16 patients without DM (NDM). All participants underwent an OCTA scan with a 3×3 mm pattern. Perfusion density (PD) were calculated All vessels PD (PDall), large vessels PD (PDlarge), and capillaries PD (PDcap) were calculated respectively. The concentrations of syndecans were measured using Luminex. Results:(1)The level of syndecan-1 in DR (298.500±106.900 pg/ml) was higher than that in NDR (193.800±51.920 pg/ml) and NDM (181.900±42.580 pg/ml) (both p<0.05). The level of syndecan-4 in DR (83.270±19.180 pg/ml) was lower than that in NDR (110.300±13.720 pg/ml) and NDM (116.900±40.570 pg/ml) (both p<0.05). (2)The PDall in DR (37.840±3.552) was lower than that in NDR (42.760±2.633) and NDM (46.460±2.201) (both p<0.05). The PDlarge, the value in DR (15.940±4.094) was higher than that in NDR (12.600±3.179) and NDM (11.850±2.565) (both p<0.05). And the PDcap in DR (21.900±4.581) was lower than that in NDR (30.150±2.521) and NDM (31.820±2.535) (both p<0.05). (3)Syndecan-1 level was negatively correlated with PDall (r=-0.5499, p<0.0001), PDcap (r=-0.4938, p=0.0005). Syndecan-4 level was positively correlated with PDall (r=0.3149, p=0.0330), PDcap (r=0.3470, p=0.0181). (4)ROC analysis showed that syndecan-1 (AUC=0.8188, p=0.0072), syndecan-4 (AUC=0.8750, p=0.0016), PDall (AUC=0.8563, p=0.0027), PDlarge (AUC=0.7625, p=0.0269), and PDcap (AUC=0.9375, p=0.0002) all demonstrated good diagnostic performance for DR. The combination of all indicators for diagnosing DR achieved an AUC of 0.9750, p<0.0001. Conclusions:The differential expression of syndecan-1 and syndecan-4 was observed in the aqueous humor of DR patients, with syndecan-1 being up-regulated and syndecan-4 down-regulated. As DR progresses, retinal large vessel PD showed an increasing trend, while capillaries PD decreased. Moreover, both syndecan-1 and syndecan-4 exhibited correlations with retinal capillaries PD. Syndecan-1, syndecan-4 and OCTA parameters had demonstrated excellent diagnostic efficacy for DR. These results not only expanded the range of potential biomarkers for detecting DR but also provide support for the future development of novel therapeutic targets for this condition.