Abstract
PURPOSE: Attenuated endothelium glycocalyx had been shown to be related to vascular damage during diabetic retinopathy (DR). Syndecans were pivotal components of retinal glycocalyx, which could be released from the endothelial surface by a highly regulated proteolytic cleavage. Thus, in the present study, we tested for the associations between diabetic retinal vascular injuries, as evidenced by optical coherence tomography angiography (OCTA) metrics, and levels of syndecan-1 and syndecan-4 in the aqueous humor of diabetic patients. METHODS: A prospectively designed cross-sectional study. The study enrolled 14 patients (16 eyes) with DR, 8 patients (10 eyes) with diabetes mellitus (DM) but no DR (NDR), and 16 patients (20 eyes) without DM (NDM). All participants underwent an OCTA scan with a 3 × 3 mm pattern. The images were meticulously binarized for quantification. OCTA metrics of perfusion density (PD) were calculated after large vessels were separated from capillaries by a rigorous automatic algorithm. All vessels PD (PD(all)), large vessels PD (PD(large)), and capillaries PD (PD(cap)) were calculated, respectively. Additionally, the concentrations of syndecans were measured using the highly sensitive Luminex Multiplex Immunoassay, ensuring the accuracy and reliability of the results. RESULTS: The aqueous humor level of syndecan-1 in DR (298.500 ± 106.900 pg./mL) group was significantly higher than that in NDR (193.800 ± 51.920 pg./mL) and NDM (181.900 ± 42.580 pg./mL) group (both p < 0.05). For syndecan-4, the level in aqueous humor in DR (83.270 ± 19.180 pg./mL) group was significantly lower than that in NDR (110.300 ± 13.720 pg./mL) and NDM (116.900 ± 40.570 pg./mL) group (both p < 0.05). But the differences of syndecan-1 and syndecan-4 had no statistical significance between NDM and NDR group (both p > 0.05). About the OCTA metrics, the PD(all) in DR (37.840 ± 3.552) group was significantly lower than that in NDR (42.760 ± 2.633) and NDM (46.460 ± 2.201) group (both p < 0.05). For the PD(large), the value in DR (15.940 ± 4.094) group was significantly higher than that in NDR (12.600 ± 3.179) and NDM (11.850 ± 2.565) group (both p < 0.05). And the PD(cap) in DR (21.900 ± 4.581) group was significantly lower than that in NDR (30.150 ± 2.521) and NDM (31.820 ± 2.535) group (both p < 0.05). But the differences of PD(all), PD(large), and PD(cap) had no statistical significance between NDM and NDR group (both p > 0.05). The results showed that syndecan-1 level in aqueous humor was negatively correlated with PD(all) (r = -0.5499, p < 0.0001), PD(cap) (r = -0.4938, p = 0.0005). However, syndecan-4 level in aqueous humor was positively correlated with PD(all) (r = 0.3149, p = 0.0330), PD(cap) (r = 0.3470, p = 0.0181). There were no correlation between syndecan-1 and syndecan-4 with PD(large) (both p > 0.05). ROC analysis showed that syndecan-1 (AUC = 0.8188, p = 0.0072), syndecan-4 (AUC = 0.8750, p = 0.0016), PD(all) (AUC = 0.8563, p = 0.0027), PD(large) (AUC = 0.7625, p = 0.0269), and PD(cap) (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. CONCLUSION: 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.