Polyol Formation in Cell Lines of Rat Retinal Capillary Pericytes and Endothelial Cells (TR-rPCT and TR-iBRB)

Kador, Peter F.; Randazzo, James; Blessing, K.; Makita, Jun; Zhang, Peng; Yu, Keming; Hosoya, Ken

doi:10.1089/jop.2008.0070

Cited by 15 publications

(21 citation statements)

References 32 publications

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“…53 After reaching confluence, the effect of hyperglycemia and its fluctuations was investigated by varying media glucose levels over a 72-h period as summarized in Fig. 1.…”

Section: Resultsmentioning

confidence: 99%

“…Although a number of animal models are available for investigating the onset and progression of DR, a majority of 53 Both rat pericyte and endothelial cells express AR; however, only the pericytes accumulate sorbitol, suggesting that the levels of AR present in endothelial cells are too low for significant sorbitol production to occur under hyperglycemic conditions. Compared with endothelial cells, culturing pericytes in serum-free media containing !…”

Section: Discussionmentioning

confidence: 99%

“…[48][49][50][51][52] Using rat retinal capillary pericyte (TR-rPCT) and endothelial (TR-iBRB) cells, we have previously reported that short-term hyperglycemia results in pericyte apoptosis that is linked to the AR-catalyzed accumulation of sorbitol and that pericytes exposed to hypoglycemia demonstrate ER stress-linked apoptotic signaling. 53 More recently, Leal et al have reported that long-term hyperglycemia induces apoptosis in retinal endothelial (TR-iBRB) cells independent of caspase activation. 54 Here, we compare the effects of hyperglycemia and its fluctuations on ER stress in TR-rPCT and TR-iBRB cells cultured either separately or together.…”

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confidence: 99%

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Response of Rat Retinal Capillary Pericytes and Endothelial Cells to Glucose

Makita

Hosoya

Zhang

et al. 2011

Journal of Ocular Pharmacology and Therapeutics

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Aim: The purpose of this study was to investigate the effects of hyperglycemia, its fluctuations, and glucose starvation on the expression of glucose-regulated protein 78/binding immunoglobulin protein (GRP78/BiP), one of the most commonly used markers of endoplasmic reticulum stress, in rat capillary pericytes and endothelial cells cultured separately and together. Methods: Conditionally immortalized rat retinal pericyte and endothelial cell lines were cultured in dishes coated with collagen type I in Dulbecco's modified Eagle's medium containing 5.5 mM glucose. For cocultures, pericytes and endothelial cells were seeded together on rat tail collagen type I-coated cell culture plates. After 24 h of initial culture, the medium was replaced with serum-free medium containing 0-100 mM glucose for periods of up to 72 h. GRP78/BiP, caspase-3, and nuclear factor-kB expression were investigated using western blots. Results: No significant increase in GRP78/BiP expression was observed when pericytes, endothelial cells, or cocultures were exposed to either 25, 50, or 100 mM glucose for 48 h compared with the control level of 5.5 mM glucose. Similarly, no change in expression of GRP78/BiP was observed when media glucose levels were reduced from either 5.5 or 25 to 1 mM. GRP78/BiP expression significantly increased when cells were cultured for 24 h in glucose-deprived medium. This was accompanied by a time-dependent increase in the expression of caspase-3 and nuclear factor-kB. Conclusion: In diabetic retinopathy, hyperglycemia has been reported to induce apoptosis in retinal capillary vascular cells, but these studies suggest that the apoptosis is not linked to the expression of GRP78/BiP, one of the most commonly used markers of endoplasmic reticulum stress. However, GRP78/BiP-linked apoptosis may play a role in vascular changes associated with retinal ischemia/reperfusion.

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“…53 After reaching confluence, the effect of hyperglycemia and its fluctuations was investigated by varying media glucose levels over a 72-h period as summarized in Fig. 1.…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Response of Rat Retinal Capillary Pericytes and Endothelial Cells to Glucose

Makita

Hosoya

Zhang

et al. 2011

Journal of Ocular Pharmacology and Therapeutics

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“…Our results suggest that the expression levels of aldose reductase might be too low in endothelial cells of rat retinal blood vessels to affect the cellular function through a significant sorbitol accumulation under hyperglycemia. The results obtained from a recent study on cell lines of rat retinal capillary pericytes and endothelial cells may support this hypothesis (25). On the other hand, in rabbit aorta and rat skeletal muscle arterioles, the polyol pathway contributes to the hyperglycemia-induced endothelial dysfunction (26 -28).…”

Section: Discussionmentioning

confidence: 87%

Hyperglycemia Impairs Acetylcholine-Induced Vasodilation of Retinal Arterioles Through Polyol Pathway–Independent Mechanisms in Rats

et al. 2010

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Abstract. We previously reported that acetylcholine (ACh)-induced vasodilation of retinal arterioles is diminished in diabetic rats; however, the underlying mechanism(s) of this phenomenon has not been fully elucidated. To determine the role of the polyol pathway in the diabetes-induced retinal vascular dysfunction, we investigated the effect of GP-1447, an inhibitor of aldose reductase, on the attenuation of ACh-induced vasodilation of retinal arterioles seen in diabetic rats. Male Wistar rats were treated with streptozotocin (STZ) and experiments were performed 2 weeks later. The STZ-treated animals were given drinking water containing 5% D-glucose to shorten the term for the development of retinal vascular dysfunction. Treatment with GP-1447 was initiated immediately after STZ treatment and continued throughout the 2-week experimental period. The attenuation of retinal vascular responses to ACh were not modified by treatment with GP-1447, whereas the aldose reductase inhibitor completely prevented diabetes-induced thinning of the retina and sorbitol accumulation in the retina and the lens. These results suggest that mechanisms that are independent of the polyol pathway may contribute to the onset of retinal endothelial dysfunction, although the pathway plays an important role in morphological changes of retina and formation of cataracts in diabetic rats.

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“…3). Intracellular accumulation of the cell membrane impermeable sorbitol in retinal pericytes, but not ECs, increases leakiness and cell death, possibly by causing osmotic stress (Kador et al, 2009;Zhang et al, 2014). Sorbitol is subsequently converted into fructose and thereafter into the highly reactive 3-deoxyglucosone, which promotes the formation of AGEs (Kashiwagi et al, 1994;Schalkwijk et al, 2004;Oyama et al, 2006;Giacco and Brownlee, 2010;Sena et al, 2012;Yoshida et al, 2012;Mapanga and Essop, 2016).…”

Section: A Diabetes Mellitusmentioning

confidence: 99%

Manipulating Angiogenesis by Targeting Endothelial Metabolism: Hitting the Engine Rather than the Drivers—A New Perspective?

et al. 2016

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Polyol Formation in Cell Lines of Rat Retinal Capillary Pericytes and Endothelial Cells (TR-rPCT and TR-iBRB)

Abstract: Although both rat retinal pericytes and endothelial cells contain AR, sorbitol accumulation and TUNEL staining primarily occur in pericytes and are inhibited by AR inhibitors.

Cited by 15 publications

References 32 publications

Response of Rat Retinal Capillary Pericytes and Endothelial Cells to Glucose

Response of Rat Retinal Capillary Pericytes and Endothelial Cells to Glucose

Hyperglycemia Impairs Acetylcholine-Induced Vasodilation of Retinal Arterioles Through Polyol Pathway–Independent Mechanisms in Rats

Manipulating Angiogenesis by Targeting Endothelial Metabolism: Hitting the Engine Rather than the Drivers—A New Perspective?

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