Norman R Harris

Louisiana State University Health Sciences Center Shreveport, Shreveport, Louisiana, United States

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Publications (44)127.42 Total impact

  • Megan N. Watts, Norman R. Harris
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    ABSTRACT: Individuals with inflammatory bowel diseases (IBD) have an elevated risk of ocular inflammation. Both the anterior and posterior eye can be affected by IBD, although posterior eye dysfunction is more likely to go undetected. Little investigative attention has been directed toward the mechanisms of ocular dysfunction with IBD; however, given the prevalence of anemia in IBD and the effects of anemia on the retina, we examined the association between retinal function (electroretinography, ERG) and the anemia induced by experimental IBD, and we tested for a potential retinal benefit of acutely attenuating anemia (via red blood cell (RBC) infusion). Colitis was induced in mice in a model involving drinking-water ingestion of dextran sodium sulfate (DSS), with untreated drinking water administered to controls. A subset of the DSS mice was infused with RBCs to attenuate the severity of the anemia induced by DSS. ERG signals (a-waves, b-waves, and oscillatory potential amplitudes and implicit times) were compared between the three groups of mice to evaluate retinal function. ERG amplitudes were significantly decreased in DSS mice compared to controls, with the amplitudes demonstrating a positive correlation with hematocrit, that is, the lowest ERG amplitudes were found with the most severe cases of anemia. An acute infusion of RBCs into DSS mice provided an improvement in the oscillatory potential implicit times, but no significant improvements in other ERG parameters. Despite the association between anemia and ERG signals in DSS-induced colitis, acute RBC infusion may only partially attenuate the associated retinal dysfunction.
    Pathophysiology. 01/2014;
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    Randa S. Eshaq, William S. Wright, Norman R. Harris
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    ABSTRACT: Retinal tissue receives its supply of oxygen from two sources - the retinal and choroidal circulations. Decreases in retinal blood flow occur in the early stages of diabetes, with the eventual development of hypoxia thought to contribute to pathological neovascularization. Oxygen consumption in the retina has been found to decrease in diabetes, possibly due to either a reduction in neuronal metabolism or to cell death. Diabetes also enhances the rate of conversion of oxygen to superoxide in the retina, with experimental evidence suggesting that mitochondrial superoxide not only drives the overall production of reactive oxygen species, but also initiates several pathways leading to retinopathy, including the increased activity of the polyol and hexosamine pathways, increased production of advanced glycation end products and expression of their receptors, and activation of protein kinase C.
    Redox Biology. 01/2014;
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    ABSTRACT: Ocular disease is known widely to occur in a subset of patients experiencing inflammatory bowel diseases. Although this extraintestinal manifestation has been recognized for a number of years, the pathogenetic mechanisms responsible for this distant organ inflammatory response are unknown. In the current study, we used a T-cell transfer model of chronic colitis in mice in which we quantified colonic inflammation, ocular function (electroretinography), ocular blood flow (intravital microscopy of the retina), intraocular pressure, and retinal hypoxia. Ocular function in colitic mice was significantly impaired, with decreases in retinal b-wave amplitudes and oscillatory potentials. Moreover, retinal a waves and oscillatory potentials were delayed. Retinal blood flow was significantly reduced in the colitic mice, and this decrease in perfusion coupled with significant decreases in hematocrit would decrease oxygen delivery to the eye. Accordingly, mice with severe colitis showed increased levels of immunostaining for the hypoxia-dependent probe pimonidazole. Finally, intraocular pressures were found to be reduced in the colitic mice. Ocular disease occurs in a mouse model of chronic colitis, with retinal dysfunction seeming to be related to insufficient perfusion and oxygen delivery.
    Inflammatory Bowel Diseases 07/2013; · 5.12 Impact Factor
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    ABSTRACT: Patients with inflammatory bowel disease suffer not only from gut inflammation, but also from extraintestinal manifestations of the disease, including ocular pathology. The mechanisms causing ocular inflammation in these patients are unknown. The purpose of the current study was to investigate the possible vascular changes occurring in the retina using a mouse model of acute colitis, that is, ingestion of dextran sodium sulfate (DSS). Intravital microscopy of anesthetized mice revealed that DSS caused a significant 30-40% decrease in retinal red blood cell velocities, and a 45% decrease in total retinal blood flow, but no changes in intraocular pressure. To determine whether the decreases in retinal perfusion could be inhibited by an angiotensin II receptor antagonist, losartan was administered by eye drops in a subset of the mice prior to the intravital microscopy measurements. Topical losartan was able to largely attenuate the altered hemodynamics induced by DSS. We conclude that angiotensin II might be a possible target for reducing the vascular changes occurring distantly in the eye during colitis.
    Experimental Eye Research 07/2013; · 3.03 Impact Factor
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    ABSTRACT: PURPOSE: Reports of altered retinal blood flow in experimental models of type I diabetes have provided contrasting results, which leads to some confusion as to whether flow is increased or decreased. The purpose of this study was to evaluate early diabetes-induced changes in retinal blood flow in diabetic rats, using two distinctly different methods. METHODS: Diabetes was induced by injection of streptozotocin (STZ), and retinal blood flow rate was measured under anesthesia by a microsphere infusion technique, or by an index of flow based on the mean circulation time between arterioles and venules. Measurements in STZ rats were compared to age-matched non-diabetic controls. In addition, the retinal distribution of fluorescently labeled red blood cells (RBCs) was viewed by confocal microscopy in excised flatmounts. RESULTS: Retinal blood flow rate was found to decrease by ~33% in the STZ rats compared to controls (p<0.001) as assessed by the microsphere technique. However, in striking contrast, the mean circulation time through the retina was found to be almost 3× faster in the STZ rats (p<0.01). This contradiction could be explained by flow redistribution through the superficial vessels of the diabetic retina, with this possibility supported by our observation of significantly fewer RBCs flowing through the deeper capillaries. CONCLUSIONS: We conclude that retinal blood flow rate is significantly reduced in the diabetic rat, with a substantial decrease of flow through the capillaries due to shunting of blood through the superficial layer, allowing rapid transit from arterioles to venules.
    Investigative ophthalmology & visual science 04/2013; 13. · 3.43 Impact Factor
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    ABSTRACT: BACKGROUND:: Approximately one-half of patients with inflammatory bowel disease (IBD) suffer from anemia, with the most prevalent cause being iron deficiency. Accompanying the anemia are increases in erythropoietin, a plasma protein that can initiate the feedback production of new red blood cells. Anemia also occurs in animal models that are used to investigate the mechanisms of IBD; however, the extent to which iron deficiency produces the anemia in these animal models is unknown. Also unknown in the different animal models of IBD is whether the anemia upregulates the production of erythropoietin or, alternatively, whether a decrease in erythropoietin contributes to the induction of anemia. METHODS:: Two mouse models of colitis were used in this study: (1) acute 6-day ingestion of dextran sodium sulfate and (2) T-cell transfer into lymphopenic recipient mice. Measurements included indices of colitis severity, hematocrit, blood hemoglobin, plasma erythropoietin, serum iron concentration, plasma iron-binding capacities, transferrin saturation, and tissue iron concentrations. RESULTS:: Both models of colitis induced significant decreases in hematocrit, blood hemoglobin, and transferrin saturation, with the spleen and liver showing a decrease in iron content in the T-cell transfer model. Additionally, both models of colitis demonstrated significant increases in plasma erythropoietin and plasma iron-binding capacities. CONCLUSIONS:: The measurements of iron, whether in acute (dextran sodium sulfate) or chronic (T-cell transfer) models of colitis, were generally consistent with iron-deficient anemia, with large increases in erythropoietin indicative of tissue hypoxia. These changes in animal models of colitis are similar to those found in human IBD.
    Inflammatory Bowel Diseases 04/2013; · 5.12 Impact Factor
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    ABSTRACT: : Patients with inflammatory bowel disease are susceptible to microvascular thrombosis and thromboembolism. The increased incidence of thrombosis is accompanied by enhanced coagulation and abnormalities in platelet function. Clinical studies have revealed thrombocytosis, alterations in platelet activation, enhanced platelet-leukocyte interactions, and elevated plasma levels of prothrombotic cytokines. This study was directed toward determining whether the thrombocytosis, altered platelet functions, and enhanced platelet-leukocyte interactions observed in patients with inflammatory bowel disease can be recapitulated in the dextran sodium sulfate and T-cell transfer models of murine colonic inflammation. Flow cytometry was used to characterize platelet function in heparin-anticoagulated whole blood of control mice and in mice with colonic inflammation. Platelets were identified by characteristic light scattering and membrane expression of CD41. Thiazole orange labeling was used to differentiate between immature and mature platelets. Platelet activation was monitored using the expression of an activation epitope of GPIIb/IIIa integrin. The combination of CD41, CD45.2, Gr-1, F4/80, and isotype control antibodies was used to detect and quantify aggregates of leukocytes, neutrophils, and monocytes with platelets. Our results indicated that colonic inflammation is associated with thrombocytosis, leukocytosis, and the appearance of immature platelets. An increased number of circulating activated platelets was detected in colitic mice, along with the formation of aggregates of leukocytes (PLA), neutrophils (PNA), and monocytes (PMA) with platelets. Selectin blockade with fucoidin inhibited dextran sodium sulfate-induced PLA formation. The findings of this study indicate that many features of the altered platelet function detected in human inflammatory bowel disease can be reproduced in animal models of colonic inflammation.
    Inflammatory Bowel Diseases 03/2013; · 5.12 Impact Factor
  • Norman R Harris, Megan N Watts, Wendy Leskova
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    ABSTRACT: Alterations in retinal blood flow can contribute to, or be a consequence of, ocular disease and visual dysfunction. Therefore, quantitation of altered perfusion can aid research into the mechanisms of retinal pathologies. Intravital video microscopy of fluorescent tracers can be used to measure vascular diameters and bloodstream velocities of the retinal vasculature, specifically the arterioles branching from the central retinal artery and of the venules leading into the central retinal vein. Blood flow rates can be calculated from the diameters and velocities, with the summation of arteriolar flow, and separately venular flow, providing values of total retinal blood flow. This paper and associated video describe the methods for applying this technique to mice, which includes 1) the preparation of the eye for intravital microscopy of the anesthetized animal, 2) the intravenous infusion of fluorescent microspheres to measure bloodstream velocity, 3) the intravenous infusion of a high molecular weight fluorescent dextran, to aid the microscopic visualization of the retinal microvasculature, 4) the use of a digital microscope camera to obtain videos of the perfused retina, and 5) the use of image processing software to analyze the video. The same techniques can be used for measuring retinal blood flow rates in rats.
    Journal of Visualized Experiments 01/2013;
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    ABSTRACT: The aim of this study was to characterize the microvascular flow abnormalities and oxygenation changes that are present following six months of hyperglycemia in the diabetic Ins2(Akita) mouse. Previous studies have shown decreased retinal blood flow in the first several weeks of hyperglycemia in rodents, similar to the decreases seen in the early stages of human diabetes. However, whether this alteration in the mouse retina continues beyond the initial weeks of diabetes has yet to be determined, as are the potential consequences of the decreased flow on retinal oxygenation. In this study, male Ins2(Akita) and age-matched C57BL/6 (non-diabetic) mice were maintained for a period of six months, at which time intravital microscopy was used to measure retinal blood vessel diameters, blood cell velocity, vascular wall shear rates, blood flow rates, and transient capillary occlusions. In addition, the presence of hypoxia was assessed using the oxygen-sensitive probe pimonidazole. The diabetic retinal microvasculature displayed decreases in red blood cell velocity (30%, p<0.001), shear rate (25%, p<0.01), and flow rate (40%, p<0.001). Moreover, transient capillary stoppages in flow were observed in the diabetic mice, but rarely in the non-diabetic mice. However, no alterations were observed in retinal hypoxia as determined by a pimonidazole assay, suggesting the possibility that the decreases seen in retinal blood flow may be dictated by a decrease in retinal oxygen utilization.
    Experimental Eye Research 03/2012; 98:9-15. · 3.03 Impact Factor
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    ABSTRACT: The purpose of this study was to investigate the influence of glutathione on the electroretinogram (ERG) in diabetic and non-diabetic rats. Streptozotocin (STZ: 60 mg/kg) was injected into male RCC Wistar rats to induce hyperglycemia, with buffer instead of STZ injected into age-matched non-diabetic controls. After 8 weeks, ERG measurements were obtained at seven different scotopic flash intensities on the two groups of anesthetized, dark-adapted rats (controls, STZ). Following ERG measurements, eyes were enucleated for measurements of retinal/vitreous GSH and glutathione disulfide (GSSG). Diabetic rats produced delayed b-wave ERG signals (increased implicit times), but had normal a-wave and b-wave amplitudes, a-wave implicit times, and oscillatory potentials. No differences were observed in retinal GSH or GSSG between controls and diabetics; however, correlations between GSH and all ERG parameters (with the exception of b-wave implicit times) were noted, and were not significantly altered by the presence of hyperglycemia. GSH is likely to play an important role in retinal function as assessed by the ERG, with this role not substantially altered in rats diabetic for 8 weeks.
    Current eye research 09/2011; 36(9):831-7. · 1.51 Impact Factor
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    ABSTRACT: Hypoxia and the associated hypoxia-inducible factors (HIFs) may be influential in the progression of diabetic retinopathy. However, little is known of the extent of hypoxia and the levels of HIFs early in the progression of the disease. In the current study, we injected the oxygen-dependent probe pimonidazole (Hypoxyprobe™-1) into diabetic rats, and also performed immunohistochemistry to determine the retinal levels of HIF-1α and HIF-2α. The rats were made diabetic using a single injection of streptozotocin (STZ; 60 mg/kg), with vehicle-injected rats used as non-diabetic controls. The measurements of hypoxia and HIF levels were obtained three weeks following STZ injection, at which time we have previously found significant decreases in retinal blood flow in the same model. In the current experiments, no increases in either HIF-1α or hypoxia were observed in the diabetic rats (compared with controls), and there was even a tendency for hypoxia levels to be decreased (tissue more highly oxygenated). However, we did observe an increase in HIF-2α in the retinas of the diabetic rats. Therefore, we conclude that early diabetes-induced increases in HIF-2α occur independently of hypoxia.
    Experimental Eye Research 06/2011; 93(4):437-41. · 3.03 Impact Factor
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    ABSTRACT: The mechanisms by which microvascular alterations contribute to the pathogenesis of the inflammatory bowel diseases (IBDs; Crohn's disease, ulcerative colitis) have not been clearly delineated. The purpose of the current study was to characterize the inflammatory events, microvascular alterations, and blood cell changes that occur in a mouse model of IBD. In this model, CD4(+) T-lymphocytes obtained from interleukin-10-deficient mice were injected intraperitoneally into lymphopenic, recombinase-activating gene-1 deficient (RAG(-/-)) mice. Two groups of control mice were also included: RAG(-/-) mice and C57BL/6 mice that were injected with phosphate-buffered saline but did not receive the T-cells. Four weeks later, the RAG(-/-) mice that had received the T-cell transfer showed significant signs of colonic inflammation, but without significant decreases in either body weight or mean arterial blood pressure. T-cell transfer increased the volume % of circulating platelets, while decreasing the number of circulating red blood cells. Additionally, the T-cell transfer tended to increase the circulating numbers of both lymphocytes and neutrophils when compared to unmanipulated RAG(-/-) mice. First-order colonic arterioles and venules tended to dilate in the colitic mice; however, the dilation was considerably more substantial with higher numbers of circulating leukocytes. The possibility that circulating inflammatory cells initiate the microvascular alterations in colitis warrants further investigation.
    Pathophysiology 06/2011; 18(4):305-11.
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    ABSTRACT: The mechanisms of early diabetes-induced decreases in retinal blood flow have yet to be fully determined. The aim of this study was to explore the hypothesis that 20-hydroxyeicosatetraenoic acid (20-HETE) plays a role in the early decrease of retinal hemodynamics in diabetic mice. 20-HETE has been implicated previously in the diabetes-enhanced vasoconstriction of mesenteric and renal vessels; however, its role in the diabetic retinal microcirculation has not been investigated. Diabetes was induced by multiple low-dose injections of streptozotocin (STZ; 50 mg/kg for 5 consecutive days), then ∼2 weeks later the mice were administered daily intraperitoneal injections with or without the 20-HETE inhibitor HET0016 (2.5 mg/kg/day) for the following 2 weeks. Non-diabetic age-matched mice were included as controls. Intravital microscopy was used to obtain measurements of retinal vascular diameters and red blood cell (RBC) velocities for the feed arterioles and draining venules extending out of and into the optic disk. From these values, wall shear rates and blood flow rates were calculated. Diabetes induced approximately 30-40% decreases in RBC velocity, wall shear rate, and blood flow rate. These decreases were attenuated to 5-10% in the mice given HET0016. In summary, the 20-HETE inhibitor HET0016 is able to attenuate the retinal hemodynamic changes induced by diabetes.
    Experimental Eye Research 05/2011; 93(1):108-13. · 3.03 Impact Factor
  • Amit Singh Yadav, Norman R Harris
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    ABSTRACT: The purpose was to investigate the effect of the superoxide dismutase mimetic tempol on decreases in retinal blood flow that are found in diabetic mice. Streptozotocin (STZ) was injected into male C57BL/6 mice to induce hyperglycemia. One week following the STZ injection, subsets of the mice were given drinking water with or without 1 mM tempol for an additional three weeks. At the end of the four-week protocol, microvascular parameters were quantified via intravital microscopy, and included measurements of retinal diameters, red blood cell (RBC) velocities, blood flow rates, and wall shear rates. Diabetes induced ~40-45% decreases in retinal blood flow rate (p < 0.001) four weeks following injection of STZ. The decrease in blood flow rate occurred with decreases in microvascular diameters (D) and RBC velocities (V). The average percentage decrease in velocity was greater than the percentage decrease in diameter and, therefore, wall shear rates (= 8 V/D) were ~25% lower in the diabetics than in the non-diabetics (p < 0.05). A three-week administration of tempol in the STZ mice allowed significantly higher blood flow rates than in the untreated STZ mice, with RBC velocities improved by the antioxidant (p < 0.05 on the venular side). However, tempol provided only moderate (and not statistically significant) improvements in wall shear rates. The antioxidant tempol provides partial improvements in retinal microvascular hemodynamics early in the progression of STZ-induced diabetes in mice.
    Current eye research 05/2011; 36(5):456-61. · 1.51 Impact Factor
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    ABSTRACT: In the current study of murine colitis, the potential roles of thromboxane and the thromboxane-prostanoid (TP) receptor were investigated, in as much as thromboxane signaling has been implicated in human inflammatory bowel disease. Colitis was induced in C57BL/6 mice via ingestion of dextran sodium sulfate (DSS), with or without co-administration of the thromboxane synthase inhibitor ozagrel (25 mg/kg/day) or the TP receptor antagonist vapiprost (2.5 mg/kg/day). Immunohistochemistry of colonic tissue demonstrated a DSS-induced increase in TP receptor expression, but not of thromboxane synthase. Moreover, tissue levels of the metabolite thromboxane B(2) were unchanged by DSS. Vapiprost, but not ozagrel, partially attenuated histologic signs of inflammation induced by DSS, with vapiprost allowing a smaller increase in colon weight per unit length than ozagrel. Vapiprost also tended to attenuate DSS-induced alterations in intestinal transit. In summary, TP receptor antagonism was more effective than thromboxane synthase inhibition in alleviating DSS-induced colitis in mice.
    Agents and Actions 01/2011; 60(1):87-92. · 1.59 Impact Factor
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    ABSTRACT: Hyperglycemia mediates endothelial cell dysfunction through a number of potential mechanisms that could result in the decrease of retinal blood flow early in diabetes. The aim of this study was to explore the role of endothelin receptor A (ET(A)) in the early decrease of retinal blood flow in diabetic mice. Diabetes was induced by streptozotocin, then ∼1 wk later the mice were administered drinking water with or without the ET(A) receptor antagonist atrasentan (7.5mg/kg/day) for the following 3 weeks. Non-diabetic age-matched mice with or without atrasentan were included as controls. For each mouse, measurements of retinal vascular diameters and red blood cell (RBC) velocities were obtained via intravital microscopy for the 5-7 feed arterioles (and draining venules) extending out of (and into) the optic disk, and from these values, flow rates and wall shear rates were calculated. Additionally, the number of retinal capillaries was counted by fluorescent immunostaining of platelet-endothelial cell adhesion molecule-1 (PECAM-1). Diabetes induced statistically significant decreases in RBC velocity, flow rate, and wall shear rate, with these alterations partially inhibited by atrasentan. No changes were observed in PECAM-1 expression among groups. The changes induced by diabetes, and the attenuation provided by atrasentan, were greater in the smaller retinal arterioles. In summary, ET(A) appears to play a role in the early decreases in retinal blood flow in a mouse model of diabetes.
    Experimental Eye Research 11/2010; 91(5):670-5. · 3.03 Impact Factor
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    ABSTRACT: Hypoxia has been reported to be associated with the colonic inflammation observed in a chemically induced mouse model of self-limiting colitis, suggesting that low tissue oxygen tension may play a role in the pathophysiology of inflammatory tissue injury. However, no studies have been reported evaluating whether tissue hypoxia is associated with chronic gut inflammation. Therefore, the objective of the present study was to determine whether hypoxia is produced within the colon during the development of chronic gut inflammation. Adoptive transfer of CD4(+) T cells obtained from interleukin-10-deficient (IL-10(-/-)) mice into lymphopenic recombinase-activating gene-1-deficient (RAG(-/-)) mice induces chronic colonic inflammation, with the inflammation ranging from mild to severe as determined by blinded histological analyses. Colonic blood flow, hematocrit, and vascular density were determined using standard protocols, whereas tissue hypoxia was determined using the oxygen-dependent probe pimonidazole. Adoptive transfer of IL-10(-/-) CD4(+) T cells into RAG(-/-) recipients induced chronic colonic inflammation that ranged from mild to severe at 8 weeks following T-cell transfer. The colitis was characterized by bowel wall thickening, goblet cell dropout, and inflammatory infiltrate. Surprisingly, we found that animals exhibiting mild colonic inflammation had increased hypoxia and decreased systemic hematocrit, whereas mice with severe colitis exhibited levels of hypoxia and hematocrit similar to healthy controls. In addition, we observed that the extent of hypoxia correlated inversely with hematocrit and vascular density. Changes in hematocrit, vascular density, and inflammatory state appear to influence the extent of tissue oxygenation in the T-cell-mediated model of chronic gut inflammation.
    Inflammatory Bowel Diseases 09/2010; 17(3):742-6. · 5.12 Impact Factor
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    ABSTRACT: Decreases in retinal blood flow in diabetics could render the retina hypoxic. In mouse and rat models of diabetes, a decrease in retinal blood flow occurs early, within 3-4 weeks of the induction of hyperglycemia, although information is scarce on whether this early decrease in flow induces hypoxia. The purpose of the current study was to determine whether hypoxia-inducible factor (HIF) levels increase following 4 and/or 12 weeks of hyperglycemia in streptozotocin (STZ)-injected mouse (C57BL/6) and rat (Wistar) retinas. Additionally, retinal tissue hypoxia was measured with pimonidazole following 12 weeks of hyperglycemia. These aims were accomplished via immunostaining of cross-sections from enucleated eyes. In mice, staining for HIF-1alpha and HIF-2alpha showed a contrasting pattern, with HIF-1alpha higher in the inner retina than outer, but HIF-2alpha higher in the outer retina than inner. However, in rats, staining for both HIF-1alpha and HIF-2alpha was more intense in the inner retina. The HIF-1alpha staining intensities and patterns were similar between diabetic animals and their non-diabetic counterparts following 4 and 12 weeks of hyperglycemia. The same was true for HIF-2alpha except for a trend toward an increase following 12 weeks of hyperglycemia in mice. Pimonidazole staining showed significant decreases throughout all layers of the central retina and most layers of the peripheral retina of rats (but not mice), following 12 weeks of hyperglycemia. In summary, despite early decreases in flow in rats and mice, retinal HIF-1alpha and HIF-2alpha were not found to be increased, and the extent of hypoxia may even decrease after 12 weeks of hyperglycemia in rats.
    Experimental Eye Research 12/2009; 90(3):405-12. · 3.03 Impact Factor
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    ABSTRACT: Adoptive transfer of naive T-lymphocyte subsets into lymphopenic mice initiates chronic gut inflammation that mimics several aspects of inflammatory bowel disease (IBD). Patients with IBD can have profound alterations in intestinal blood flow, but whether the same is true in the T-cell transfer model has yet to be determined. In the current study, chronic intestinal inflammation was induced in recombinase-activating gene-1-deficient (RAG(-/-)) mice by adoptive transfer of CD4(+) T-lymphocytes obtained from interleukin-10 deficient (IL-10(-/-)) mice. Four weeks later, widespread colonic inflammation was observed in the reconstituted recipients, in contrast to 2 control sets of mice injected with a different subset of lymphocytes or with vehicle alone. We observed that the resulting pathology induced in the reconstituted RAG(-/-) mice was divided distinctly into 2 subsets: 1 with blood flow near normal with very high inflammation scores, and the other with severely attenuated blood flow but with much lower signs of inflammation. Colonic and ileal blood flow rates in the latter subset of CD4(+) mice averaged only approximately 30% compared to the mice with higher inflammation scores. The lower blood flow rates were associated with greatly reduced red blood cell concentrations in the tissue, suggesting a possible loss of vascular density. In this model of chronic intestinal inflammation, mild inflammation was associated with significant decreases in blood flow.
    Inflammatory Bowel Diseases 10/2009; 16(5):776-82. · 5.12 Impact Factor
  • Kavitha Nellore, Norman R Harris
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    ABSTRACT: Arteriolar tone is partially controlled by diffusing mediators released by closely paired venules and is reported to depend on venular shear and venular leukocyte adherence. In healthy rat mesentery, venule-initiated arteriolar dilation and consequent enhanced capillary flow appear to be tightly regulated by nitric oxide (NO). In contrast, diabetes inhibits NO-dependent vasodilation and is associated with dysfunctional microcirculation. The objective of this study was to investigate venule-dependent NO in diabetes. Arteriolar and venular wall concentrations of NO were measured in control and diabetic (streptozotocin-induced) rat mesentery with fluorescent diaminofluorescein-2-diacetate (DAF-2-DA); tissue NO was measured with DAF-2. Venular leukocyte adherence and microvascular shear rates were also measured. Microvascular NO in diabetic rats was found to be significantly lower (<50%) than in controls. In normal rats, arteriolar NO demonstrated a positive correlation with venular NO and venular shear, and a negative correlation with venular leukocyte adherence. Diabetes eliminated all these correlations. No correlation was present between arteriolar NO and arteriolar shear in either normal or diabetic rats. Arteriolar NO appears to be enhanced by venular shear in normal but not in diabetic rats. This dysfunction could contribute to poor capillary perfusion in diabetes.
    Microcirculation 07/2009; 11(5):415-23. · 2.76 Impact Factor

Publication Stats

322 Citations
127.42 Total Impact Points

Institutions

  • 2005–2014
    • Louisiana State University Health Sciences Center Shreveport
      • Department of Pathology
      Shreveport, Louisiana, United States
  • 2005–2009
    • Louisiana State University in Shreveport
      Shreveport, Louisiana, United States
  • 2001–2009
    • Pennsylvania State University
      • Department of Bioengineering
      University Park, MD, United States