NAD⁺-Induced Vasotoxicity in the Pericyte-Containing Microvasculature of the Rat Retina: Effect of Diabetes

Abstract

Purinergic vasotoxicity triggered by extracellular NAD(+) is a newly recognized mechanism that may contribute to the cell death observed in the pericyte-containing microvascular of the diabetic retina.

The P2X7 Receptor Channel: Recent Developments and the Use of P2X7 Antagonists in Models of Disease

“…These NAD-induced P2X7 responses are observed in T cells, but they are not observed in macrophages (Adriouch et al, 2001;Hong et al, 2009). However, although the majority of studies investigating NADinduced activation of P2X7 have been performed with murine T cells, there is also evidence that this pathway occurs in murine astrocytes and rat retinal microvessels (Liao and Puro, 2006). Although NAD induces similar downstream events to that seen after ATP-induced activation of P2X7, much lower NAD concentrations are required for receptor activation compared with ATP (EC 50 for phosphatidylserine exposure 2 and 100 mM, respectively) (Seman et al, 2003).…”

Purinergic signaling in retinal degeneration and regeneration

“…High extracellular ATP causes cellular death in the pericyte-containing retinal microvasculature by activation of P2X 7 resulting in cell depolarization and lethal calcium influx through voltage-gated calcium channels (Sugiyama et al, 2005). Diabetes boosts the vulnerability of retinal microvessels to the lethal effect of P2X 7 activation, i.e., the agonist concentration required to trigger lethal transmembrane pore formation decreases markedly soon after the onset of diabetes (Sugiyama et al, 2004; 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 Liao and Puro, 2006). The purinergic vasotoxicity may result in reduced retinal blood flow and disrupted vascular function in the diabetic retina (Sugiyama, 2014).…”

Evaluation of YO-PRO-1 as an early marker of apoptosis following radiofrequency ablation of colon cancer liver metastases

“…Chagnon et al (2010) added YP1 directly to lung tissues within anesthetized mice to study cell survival following acute lung injury. YP1 staining performed in gastric glands, pieces of dissected skin, and isolated retina samples from mice and rats has resulted in the identification of a clear distinction between live and apoptotic cells (Ito et al 2010;Kohler et al 2010;Liao and Puro 2006). Other investigators have cultured hepatocyte spheroids and convincingly determined apoptotic cells using YP1 (Castañeda and Kinne 2000;Higashiyama et al 2003).…”