In a high-glucose condition or diabetes, pericytes exhibit altered biochemical and molecular changes. Pericytes upregulate synthesis of basement membrane components,
30 48 reduce structural support of vascular walls,
49 50 51 and inhibit contractile action that can modulate blood flow.
52 53 High glucose may inhibit pericyte contractility
52 by regulating Na
+/K
+-adenosine triphosphatase (ATPase) activity. Investigators have shown that vascular smooth muscle cells (VSMCs) grown in high glucose exhibit decreased Na
+ and K
+ transport and alter membrane permeability to cations, possibly leading to changes in contractility and proliferation.
54 Regulation of Na
+ and K
+ levels is to a large extent controlled by GJIC. For example, gap junctions between glial cells allow intercellular exchange of Na
+ and equalize intracellular concentrations of Na
+.
55 The association between GJIC and Na
+/K
+-ATPase activity has been reported in other cell types.
56 Pericyte contractility has been shown to be dependent on the presence of adenosine triphosphate (ATP),
57 58 which is necessary for ATPase activity. Recent studies indicate that not only does Na
+ and K
+ ions pass through gap junctions but also the transfer of ATP between gap junction channels. Previous studies have shown that labeled nucleotides transfer through gap junctions of pericytes
1 and that ATP transfer to adjacent cells is 300 times greater through channels formed by Cx43 than through channels formed by other connexins.
59 Moreover, studies have indicated altered levels of retinal Na
+, K
+-ATPase in streptozotocin-induced diabetic rats,
60 which may be associated with altered GJIC in diabetes. Overall, high glucose-induced reduction in GJIC may have a profound effect on pericyte contractility and other physiologic functions. Further studies are needed, to understand the role of connexin expression in the maintenance of retinal vascular homeostasis. A challenge for future studies is to explore the pathophysiological consequences of defective cell–cell communication in diabetic retinopathy.