title: Reduction of experimental diabetic vascular leakage and pericyte apoptosis in mice by delivery of αA-crystallin with a recombinant adenovirus.
abstract: OBJECTIVE
  The study aimed to evaluate the efficacy of recombinant adenovirus expressing αA-crystallin (Ad-αAc-Gfp) in reducing pericyte loss within retinal vasculature in early diabetes.
  
  
  METHODS
  Diabetes was induced by streptozotocin injection into C57BL/6 mice. Ad-αAc-Gfp was delivered by intravitreous injection to the right eyes of mice 2 weeks before induction of diabetes. Vascular leakage was determined by fluorescent angiography, Evans Blue leakage assay and leucocyte adhesion test. Production of αA-crystallin was analysed by immunoblotting and double immunostaining and pericyte loss was analysed by pericyte count.
  
  
  RESULTS
  Vessel leakage and pericyte loss were observed in the streptozotocin-induced diabetic retina. Decreased abundance of αA-crystallin in retinas 2 and 6 months after the induction of diabetes was confirmed by two-dimensional electrophoretic analysis, immunoblotting and RT-PCR. Double immunofluorescence staining for αA-crystallin and NG2 chondroitin sulphate proteoglycan revealed that αA-crystallin was predominantly produced in the retinal pericyte and that the number of αA-crystallin-producing pericytes decreased in the diabetic retina. Retinal infection with Ad-αAc-Gfp led to decreased pericyte loss and vascular leakage compared with control.
  
  
  CONCLUSIONS
  Intravitreal delivery of Ad-αAc-Gfp protects against vascular leakage in the streptozotocin-induced model of diabetes. This effect is associated with the inhibition of diabetic retinal pericyte loss in early diabetes, suggesting that αA-crystallin has a role in preventing the pathogenesis of early diabetic retinopathy.
authors: Department of Anatomy and Neurobiology, Medical Research Center for Neural Dysfunction, Institute of Health Science, School of Medicine, Gyeongsang National University, 92 Chilam-dong, Jinju, Gyeongnam, 660-751, Republic of Korea.
authors: Y H
authors: YH
authors: Kim
authors: Department of Anatomy and Neurobiology, Medical Research Center for Neural Dysfunction, Institute of Health Science, School of Medicine, Gyeongsang National University, 92 Chilam-dong, Jinju, Gyeongnam, 660-751, Republic of Korea.
authors: S Y
authors: SY
authors: Park
authors: Department of Anatomy and Neurobiology, Medical Research Center for Neural Dysfunction, Institute of Health Science, School of Medicine, Gyeongsang National University, 92 Chilam-dong, Jinju, Gyeongnam, 660-751, Republic of Korea.
authors: J
authors: J
authors: Park
authors: Department of Anatomy and Neurobiology, Medical Research Center for Neural Dysfunction, Institute of Health Science, School of Medicine, Gyeongsang National University, 92 Chilam-dong, Jinju, Gyeongnam, 660-751, Republic of Korea.
authors: Y S
authors: YS
authors: Kim
authors: Center for Functional Connectomics, Korea Institute of Science and Technology, Seoul, Republic of Korea.
authors: E M
authors: EM
authors: Hwang
authors: Department of Physiology, School of Medicine, Gyeongsang National University, Jinju, Republic of Korea.
authors: J Y
authors: JY
authors: Park
authors: Department of Anatomy and Neurobiology, Medical Research Center for Neural Dysfunction, Institute of Health Science, School of Medicine, Gyeongsang National University, 92 Chilam-dong, Jinju, Gyeongnam, 660-751, Republic of Korea.
authors: G S
authors: GS
authors: Roh
authors: Department of Anatomy and Neurobiology, Medical Research Center for Neural Dysfunction, Institute of Health Science, School of Medicine, Gyeongsang National University, 92 Chilam-dong, Jinju, Gyeongnam, 660-751, Republic of Korea.
authors: H J
authors: HJ
authors: Kim
authors: Department of Anatomy and Neurobiology, Medical Research Center for Neural Dysfunction, Institute of Health Science, School of Medicine, Gyeongsang National University, 92 Chilam-dong, Jinju, Gyeongnam, 660-751, Republic of Korea.
authors: S S
authors: SS
authors: Kang
authors: Department of Anatomy and Neurobiology, Medical Research Center for Neural Dysfunction, Institute of Health Science, School of Medicine, Gyeongsang National University, 92 Chilam-dong, Jinju, Gyeongnam, 660-751, Republic of Korea.
authors: G J
authors: GJ
authors: Cho
authors: Department of Anatomy and Neurobiology, Medical Research Center for Neural Dysfunction, Institute of Health Science, School of Medicine, Gyeongsang National University, 92 Chilam-dong, Jinju, Gyeongnam, 660-751, Republic of Korea. choiws@gnu.ac.kr.
authors: W S
authors: WS
authors: Choi
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005947:Glucose / Q000494:pharmacology; D058449:Intravitreal Injections; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020286:Pericytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D013311:Streptozocin / Q000009:adverse effects; D016896:Treatment Outcome; D038202:alpha-Crystallin A Chain / Q000008:administration & dosage / Q000235:genetics* / Q000378:metabolism
chemical_list: D038202:alpha-Crystallin A Chain; D013311:Streptozocin; D005947:Glucose