Anti-CXCL10 monoclonal antibody therapy protects against the diabetic retinopathy in the mouse model induced by streptozotocin.

Abstract

OBJECTIVE:

To explore the effect of CXC chemokine CXCL10 in the mice with diabetic retinopathy (DR).

METHODS:

DR models were constructed on mice via injection of streptozotocin (STZ). At 3 weeks of STZ, mice were treated with anti-CXCL10 monoclonal antibodies (mAb)/control mAb, and a series of experiments were then conducted at 6 weeks of STZ, including HE staining, western blotting, retinal trypsin digestion, real-time qPCR and enzyme-linked immuno sorbent assay (ELISA). The corresponding kits were used to detect the activity of oxidative stress markers.

RESULTS:

Compared with nondiabetic eyes, DR mice both at 3 and 6 weeks presented the decreases in the total retinal thickness, the retinal outer nuclear layer (ONL) thickness, and the cells of ganglion cell layer (GCL), with the upregulated CXCL10, pro-inflammatory cytokines and malondialdehyde (MDA), as well as the downregulated levels of superoxide dismutase (SOD), glutathione peroxidase (GPx) and CAT, especially in those at 6 weeks, which were attenuated by the anti-CXCL10 mAb treatment. Moreover, in comparison with the DR mice, mice in the DR + anti-CXCL10 mAb group gained the significant decrease in the number of acellular capillaries of retina, with up-regulations of Claudin-5 and ZO-1 and down-regulations of VEGF and FGF-2. The DR mice injected with anti-CXCL10 mAb demonstrated alleviated retinal pathology as compared to mice at 3 weeks of STZ.

CONCLUSION:

Anti-CXCL10 mAb could mitigate the retinal pathology of DR mice, with the decreased inflammation and oxidative stress, thus mediating a delay in the development or disease improvement in patients of DR.

• Authors: Zhao-Hui Sun, Fang Li, Yun-Fei Li, Min Wang, Ya-Nan Li, Li Li, Hua Yu, Guang-Xian Tang, Rui-Xue Sun
• Journal: Tissue & cell (Tissue Cell) Vol. 76 Pg. 101745 (Jun 2022) ISSN: 1532-3072 [Electronic] Scotland
• PMID: 35276554 (Publication Type: Journal Article)
• Copyright: Copyright © 2022. Published by Elsevier Ltd.

Chemical References

• Antibodies, Monoclonal
• Streptozocin

Topics

• Animals
• Antibodies, Monoclonal (adverse effects)
• Diabetes Mellitus, Experimental (drug therapy, pathology)
• Diabetic Retinopathy (drug therapy, pathology, prevention & control)
• Disease Models, Animal
• Humans
• Mice
• Retina
• Streptozocin (adverse effects)