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Increased intraretinal PO2 in short-term diabetic rats.

ABSTRACT: In diabetic retinopathy, neovascularization is hypothesized to develop due to hypoxia in the retina. However, evidence for retinal hypoxia is limited, and the progressive changes in oxygenation are unknown. The objective of this study was to determine if retinal hypoxia occurs early in the development of diabetes. Intraretinal oxygen (PO2) profiles were recorded with oxygen-sensitive microelectrodes in control and diabetic Long-Evans rats at 4 and 12 weeks after induction of diabetes. Diabetes did not affect oxygen consumption in the photoreceptors in either dark or light adaptation. Oxygenation of the inner retina was not affected after 4 weeks of diabetes, although vascular endothelial growth factor levels increased. At 12 weeks, average inner retinal PO2, normalized to choriocapillaris PO2, was higher in diabetic rats than in age-matched controls, which was opposite to what was expected. Thus retinal hypoxia is not a condition of early diabetes in rat retina. Increased inner retinal PO2 may occur because oxygen consumption decreases in the inner retina.

SUBMITTER: Lau JC

PROVIDER: S-EPMC4238003 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Increased intraretinal PO2 in short-term diabetic rats.

Lau Jennifer C M JC Linsenmeier Robert A RA

Diabetes 20140715 12

In diabetic retinopathy, neovascularization is hypothesized to develop due to hypoxia in the retina. However, evidence for retinal hypoxia is limited, and the progressive changes in oxygenation are unknown. The objective of this study was to determine if retinal hypoxia occurs early in the development of diabetes. Intraretinal oxygen (PO2) profiles were recorded with oxygen-sensitive microelectrodes in control and diabetic Long-Evans rats at 4 and 12 weeks after induction of diabetes. Diabetes d ...[more]

PMID: 25028524

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Project description:IntroductionRefrigeration of platelets is considered to provide advantages in therapy of acute hemorrhage due to increased platelet responsiveness. The alleviation of inhibitory signaling caused by cold temperature (CT) has been identified as an important mechanism contributing to enhanced platelet reactivity, detectable in freshly prepared platelets within 1 h of cold storage. The aim of this study was to confirm the effects of short-term refrigeration in platelets from apheresis-derived platelet concentrates (APC).MethodsAPC were stored under standardized conditions for 1 day or for 2 days at room temperature and then refrigerated for 1 h, followed by sampling of platelets for analysis. Platelet reactivity was measured by aggregation studies using threshold concentrations of different agonists and by detection of fibrinogen binding using flow cytometry. The exploration of inhibitory signaling comprised the detection of VASP phosphorylation using flow cytometry or Western blot and the measurement of cyclic nucleotide levels.ResultsAggregation responses induced with ADP, collagen, or thrombin receptor-activating peptide-6 (TRAP-6) were increased in APC after cold storage for 1 h, associated with elevated TRAP-6-induced fibrinogen binding. VASP phosphorylation levels were decreased after cold exposition, detectable in 1-day- and 2-day-stored APC with flow cytometry, and in 2-day-stored APC with Western blot technique. Induced cGMP levels were lower after storage at CT in APC on day 1 and on day 2, whereas cAMP levels were reduced on 2-day-stored APC.ConclusionShort-term refrigeration for 1 h is sufficient to induce an attenuation of inhibitory signaling, accompanied with increased aggregation responses in APC stored for up to 2 days. The "on demand" refrigeration of PC may be a reasonable approach for the preparation of platelets with enhanced responsiveness to treat patients with hemorrhage more effectively, which should be further addressed in consecutive studies.

Project description:BACKGROUND & AIMS:Patients with diabetes have defects in the vagal afferent pathway that result in abnormal gastrointestinal function. We investigated whether selective increased activation of the 2-pore domain potassium channel TRESK (2-pore-domain weak inward-rectifying potassium channel-related spinal cord potassium channel) contributes to nodose ganglia (NG) malfunction, disrupting gastrointestinal function in diabetic rats. METHODS:We conducted whole-cell current-clamp and single-unit recordings in NG neurons from diabetes-prone BioBreeding/Worcester rats and streptozotocin-induced diabetic (STZ-D) rats and compared them with control rats. NG neurons in rats or cultured NG neurons were exposed to pharmacologic antagonists and/or transfected with short hairpin or small interfering RNAs that reduced expression of TRESK. We then made electrophysiologic recordings and studied gastrointestinal functions. RESULTS:We observed reduced input resistance, hyperpolarized membrane potential, and increased current threshold to elicit action potentiation in NG neurons of STZ-D rats compared with controls. NG neuron excitability was similarly altered in diabetes-prone rats. In vivo single-unit NG neuronal discharges in response to 30 and 60 pmol cholecystokinin octapeptide were significantly lower in STZ-D rats compared with controls. Reducing expression of the TRESK K+ channel restored NG excitability in vitro and in vivo, as well as cholecystokinin 8-stimulated secretion of pancreatic enzymes and secretin-induced gastrointestinal motility, which are mediated by vago-vagal reflexes. These abnormalities resulted from increased intracellular Ca2+ in the NG, activating calcineurin, which, in turn, bound to an nuclear factor of activated T cell-like docking site on the TRESK protein, resulting in neuronal membrane hyperpolarization. CONCLUSIONS:In 2 rate models of diabetes, we found that activation of the TRESK K+ channel reduced NG excitability and disrupted gastrointestinal functions.

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Increased intraretinal PO2 in short-term diabetic rats.

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Increased intraretinal PO2 in short-term diabetic rats.

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