Reduced connexin 43 expression and its effect on the development of vascular lesions in retinas of diabetic mice

Michael W. Bobbie, Sumon Roy, Kyle Trudeau, Stephanie J. Munger, Alexander M. Simon, Sayon Roy

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

Purpose. To examine whether diabetes-induced connexin 43 downregulation promotes retinal vascular lesions characteristic of diabetic retinopathy (DR). Methods. Two animal models, streptozotocin-induced diabetic mice and Cx43 heterozygous knockout (Cx43±) mice, were studied to directly assess whether diabetes reduces the expression of retinal Cx43, which, in turn, contributes to retinal vascular cell loss by apoptosis. Retinal Cx43 protein levels were assessed in nondiabetic control mice, diabetic mice, and Cx43± mice by Western blot analysis, and Cx43 localization and distribution in the retinal vascular cells were studied by immunostaining of retinal trypsin digests (RTDs). In parallel, RTDs were stained with hematoxylin and periodic acid Schiff to determine pericyte loss (PL) and acellular capillaries (AC), and TUNEL assays were performed to determine retinal vascular cell apoptosis. Results. Western blot analysis indicated significant reductions in retinal Cx43 protein levels in diabetic mice and Cx43± mice compared with those of nondiabetic mice. Similarly, a significant reduction in Cx43 immunostaining was observed in the retinal capillaries of diabetic mice and Cx43± mice compared with those of control mice. Both diabetic and age-matched Cx43± mice exhibited increased amount of PL, AC, and TUNEL-positive cells compared with control mice. Conclusions. Diabetes-induced inhibition of Cx43 expression contributes to vascular cell apoptosis in retinas of diabetic mice. This suggests that reduced Cx43 expression plays a critical role in the development of AC and PL associated with DR.

Original languageEnglish (US)
Pages (from-to)3758-3763
Number of pages6
JournalInvestigative Ophthalmology and Visual Science
Volume51
Issue number7
DOIs
StatePublished - Jul 1 2010

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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