title: Association of reduced Connexin 43 expression with retinal vascular lesions in human diabetic retinopathy.
abstract: Connexin 43 (Cx43) downregulation promotes apoptosis in retinal vascular cells of diabetic animal models; however, its relevance to human diabetic retinopathy has not been established. In this study, we investigated whether diabetes alters Cx43 expression and promotes retinal vascular lesions in human retinas. Diabetic human eyes (aged 64-94 years) and non-diabetic human eyes (aged 61-90 years) were analyzed in this study. Retinal protein samples and retinal capillary networks were assessed for Cx43 level by Western blot (WB) analysis and immunostaining. In parallel, retinal capillary networks were stained with hematoxylin and periodic acid Schiff to determine the extent of pericyte loss (PL) and acellular capillaries (AC) in these retinas. Cx43 protein expression was significantly reduced in the diabetic retinas compared to non-diabetic retinas as indicated by WB analysis (81 ± 11% of control). Additionally, a significant decrease in the number of Cx43 plaques per unit length of vessel was observed in the diabetic retinas compared to those of non-diabetic retinas (62 ± 10% of control; p < 0.005). Importantly, a strong inverse relationship was noted between Cx43 expression and the relative number of AC (r = -0.89; p < 0.0005), and between Cx43 expression and number of pericyte loss (r = -0.88; p < 0.0005). Overall, these results show that Cx43 expression is reduced in the human diabetic retinas and Cx43 reduction is associated with increased vascular cell death. These findings suggest that diabetes decreases retinal Cx43 expression and that the development of PL and AC is associated with reduced Cx43 expression in human diabetic retinopathy.
authors.affiliation: Departments of Medicine and Ophthalmology, Boston University School of Medicine, 650 Albany Street, Boston, MA, 02118, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tien
authors.affiliation: Departments of Medicine and Ophthalmology, Boston University School of Medicine, 650 Albany Street, Boston, MA, 02118, USA.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Muto
authors.affiliation: Departments of Medicine and Ophthalmology, Boston University School of Medicine, 650 Albany Street, Boston, MA, 02118, USA.
authors.forename: Joyce
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Stephen A Wynn Institute for Vision Research, Department of Ophthalmology and Visual Science, University of Iowa, Iowa City, IA, 52242, USA.
authors.forename: Elliott H
authors.initials: EH
authors.lastname: Sohn
authors.affiliation: Stephen A Wynn Institute for Vision Research, Department of Ophthalmology and Visual Science, University of Iowa, Iowa City, IA, 52242, USA.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Mullins
authors.affiliation: Departments of Medicine and Ophthalmology, Boston University School of Medicine, 650 Albany Street, Boston, MA, 02118, USA. Electronic address: sayon@bu.edu.
authors.forename: Sayon
authors.initials: S
authors.lastname: Roy
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D018031:Connexin 43 / Q000096:biosynthesis / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D012313:RNA / Q000235:genetics*; D012171:Retinal Vessels / Q000378:metabolism* / Q000473:pathology
chemical_list: D018031:Connexin 43; C500216:GJA1 protein, human; D012313:RNA
keywords: Cx43; Diabetes; Diabetic retinopathy; Gap junction intercellular communication; High glucose