PG545 alleviates diabetic retinopathy by promoting retinal Müller cell autophagy to inhibit the inflammatory response

Diabetic retinopathy (DR), a major cause of blindness in working-age people, is attributed to the inflammatory response of retinal Müller cells (RMCs). The heparanase inhibitor PG545 plays proautophagic and anti-inflammatory roles. Intraperitoneal injection of PG545 at a dose of 20 mg/kg/d clearly r...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2020-10, Vol.531 (4), p.452-458
Main Authors: Wang, Ying, Liu, Xiaojuan, Zhu, Linling, Li, Wendie, Li, Zhizhe, Lu, Xiting, Liu, Jie, Hua, Wenjuan, Zhou, Yamei, Gu, Yonghui, Zhu, Manhui
Format: Article
Language:English
Subjects:
Animals
Autophagy
Autophagy - drug effects
Autophagy-Related Protein 7 - genetics
Blood Glucose - metabolism
Body Weight
Cells, Cultured
Diabetes Mellitus, Experimental - complications
Diabetes Mellitus, Experimental - drug therapy
Diabetic retinopathy
Diabetic Retinopathy - drug therapy
Diabetic Retinopathy - pathology
Ependymoglial Cells - drug effects
Ependymoglial Cells - pathology
Glucose - pharmacology
Inflammatory response
Male
Mice, Inbred C57BL
Mice, Mutant Strains
PG545
Retinal Müller cell
Retinitis - drug therapy
Retinitis - pathology
Saponins - pharmacology
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Summary:Diabetic retinopathy (DR), a major cause of blindness in working-age people, is attributed to the inflammatory response of retinal Müller cells (RMCs). The heparanase inhibitor PG545 plays proautophagic and anti-inflammatory roles. Intraperitoneal injection of PG545 at a dose of 20 mg/kg/d clearly reduced diabetes-induced body weight changes and fasting blood glucose levels in mice. PG545 also mitigated the reduction in retinal thickness and the formation of microaneurysms by promoting autophagy to inhibit the inflammatory response. In vitro, PG545 stimulated autophagy to downregulate the inflammatory response in high glucose-induced primary adult mouse RMCs. These data suggest that PG545 mitigates DR by promoting RMC autophagy to inhibit the inflammatory response. •PG545 facilitates the autophagy in primary mouse retinal Müller cells (RMCs) under high glucose (HG) conditions.•PG545 inhibits inflammatory response via promoting autophagy in mouse MRCs under HG conditions.•PG545 mitigates the reduce of retinal thickness and the formation of microaneurysms in mouse diabetic model.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2020.07.134