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Thomas Tien, Tetsuya Muto, Elliott Sohn, Robert Mullins, Sayon Roy; Reduced Connexin 43 (Cx43) plays a role in the development of vascular lesions in human diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2688.
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Previous cell culture and animal model studies have shown that reduced Cx43 levels impair gap junction intercellular communication and promote apoptosis. In this study, we have 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. Protein samples and retinal trypsin digestion (RTD) were used to determine Cx43 level by Western blot (WB) analysis and immunofluorescence. Densitometry and Cx43 immunostaining were quantified using ImageJ analysis. In parallel, RTDs were stained with hematoxylin and periodic acid Schiff to determine the number of pericyte loss (PL) and acellular capillaries (AC).
Cx43 protein expression was significantly reduced in the human diabetic retinas compared to non-diabetic retinas as indicated by WB analysis (81 ± 11% of control). Furthermore, capillary networks of diabetic retinas showed significantly decreased number of Cx43 plaques per unit length of vessel as compared to those of non-diabetic retinas (56 ± 9% of control; p < 0.001). Importantly, a strong inverse relationship was found between Cx43 expression and relative number of acellular capillaries (r=-0.9; p < 0.001). Similarly, an inverse relationship was observed between Cx43 expression and number of pericyte loss (r=-0.88; p < 0.001). Overall, these results indicate that Cx43 expression is reduced in the vascular cells of human diabetic retinas, and promotes apoptotic cell death.
Findings from this study indicate that Cx43 expression is reduced in human diabetic retinas and contributes to the demise of pericytes and endothelial cells associated with early diabetic retinopathy.
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