title: The emerging roles of clusterin on reduction of both blood retina barrier breakdown and neural retina damage in diabetic retinopathy.
abstract: Previous proteomic studies revealed that intravitreous clusterin was decreased in diabetic retinopathy (DR) patients. We explored the role of clusterin in reduction of both blood retina barrier (BRB) breakdown and neural retina damage in early DR. Immunofluorescent staining of proliferated diabetic retinopathy (PDR) membranes was performed to detect endogenous clusterin, and intravitreous injection of clusterin (CLU group) or PBS (DR group) to streptozotocin-induced diabetic rats was conducted. Both qPCR and immunofluorescent staining were employed to investigate tight junction (TJ) protein. Fundus fluorescein angiography (FFA) and electroretinogram (ERG) were examined. Finally, HE and TUNEL stainings were used for neural retina assessment. Clusterin was expressed in the endothelial cells of PDR membranes. The expressions of several TJ protein genes were decreased in the retina of DR group (p<0.05), but elevated in that of CLU group (p<0.05). FFA revealed that there were several micrangium changes in the rats of the DR group but few in the CLU group. In ERG, the amplitude of b wave in DR group was significantly decreased compared to Control group (p<0.05), and the decreased b wave was partially rescued in CLU group under the highest flashlight level (p<0.05). HE and TUNEL staining of rat retina showed that both dropouts and apoptotic death of neural retina cells in diabetic rats were attenuated in CLU group. Clusterin had a promising role in reducing both BRB breakdown and neural retina damage under high glucose; the mechanism might be keeping TJ protein integrated and maintaining anti-apoptosis in early diabetic rats.
authors.affiliation: Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China.|These authors contributed equally to this work.
authors.forename: Conghui
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China.|These authors contributed equally to this work.
authors.forename: Jing
authors.initials: J
authors.lastname: Nie
authors.affiliation: Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China.
authors.forename: Le
authors.initials: L
authors.lastname: Feng
authors.affiliation: Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Luo
authors.affiliation: Tongji Eye Institute, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yao
authors.affiliation: Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D001813:Blood-Retinal Barrier / Q000187:drug effects*; D015153:Blotting, Western; D051152:Clusterin / Q000008:administration & dosage / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications*; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004596:Electroretinography; D005451:Fluorescein Angiography; D005455:Fluorescent Antibody Technique; D006801:Humans; D020287:In Situ Nick-End Labeling; D058449:Intravitreal Injections; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013311:Streptozocin / Q000633:toxicity; D062725:Tight Junction Proteins / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A
chemical_list: D051152:Clusterin; D062725:Tight Junction Proteins; D042461:Vascular Endothelial Growth Factor A; D013311:Streptozocin