Effect of Olmesartan on Leukocyte Recruitment in Choroid–Sclera Complex in Hypercholesterolemia Model

Torres, Rogil José de Almeida; Noronha, Lúcia de; Casella, Antônio Marcelo Barbante; Grobe, Sarah Fagundes; Martins, Isabela de Carvalho; Luchini, Andréa; Sturzeneker, Mário Cláudio Soares; Torres, Caroline Luzia de Almeida; Précoma, Dalton Bertolim

doi:10.1089/jop.2012.0142

Cited by 5 publications

(11 citation statements)

References 35 publications

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“…The present study corroborates the findings of earlier studies that hypercholesterolaemia may induce the same events in the choroid–sclera complex. The exacerbated expression of oxidised LDL in the choroid and sclera observed in G1 rabbits could account for the increase in the expression of chemotactic molecules ( 15 ) , such as monocyte chemoattractant protein-1, adhesion molecules ( 16 ) and intercellular adhesion molecule-1, which would induce an increase in macrophage concentrations in the choroid–sclera complex and, consequently, an increase in the thickness of the choroid and sclera as observed in the present study and in other studies ( 16 , 17 , 20 , 48 ) . From the ocular point of view, it is important to note that oxidised LDL, chemotactic molecules, adhesion molecules and macrophages are associated with the physiopathogenesis of AMD and may trigger or worsen this disease ( 2 , 9 , 10 , 46 – 49 ) .…”

Section: Discussionsupporting

confidence: 76%

Effect of flaxseed on choroid–sclera complex thickness and on LDL oxidation in the sclera, choroid and retina of diet-induced hypercholesterolaemic rabbits

Torres

Luchini²,

Both

et al. 2014

Br J Nutr

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The aim of the present study was to evaluate the effect of flaxseed on choroid -sclera complex thickness and on LDL oxidation in the sclera, choroid and retina of diet-induced hypercholesterolaemic rabbits. New Zealand male albino rabbits (n 21) were divided into two groups: group 1 (G1; n 11), fed a hypercholesterolaemic diet, and group 2 (G2; n 10), fed a hypercholesterolaemic diet enriched with flaxseed flour. The serum concentrations of total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol, TAG and fasting blood glucose were determined at the start of the experiment and on the day of killing (8th week). Choroid and sclera samples were subjected to haematoxylin -eosin (HE) staining and histomorphometric and immunohistochemical analyses with the anti-oxidised LDL antibody. Sensory retina samples were subjected to an immunohistochemical analysis with the primary monoclonal nitrotyrosine antibody. At the end of the experiment, a significant increase was observed in TC and LDL-C concentrations in G1 rabbits when compared with G2 rabbits (P¼0·008 and P¼0·02, respectively). HE staining revealed a significant increase in choroid -sclera complex thickness in G1 rabbits when compared with G2 rabbits (P,0·001). Immunohistochemical analysis of choroid and sclera samples with the anti-oxidised LDL marker revealed a significant increase in immunoreactivity in G1 rabbits when compared with G2 rabbits (P,0·001). Immunohistochemical analysis of sensory retina samples with the anti-nitrotyrosine marker revealed a significant increase in immunoreactivity in G1 rabbits when compared with G2 rabbits (P¼ 0·002). Flaxseed reduced the choroid -sclera complex thickness of diet-induced hypercholesterolaemic rabbits and the expression of oxidised LDL in the choroid -sclera complex as well as the expression of nitrotyrosine in the sensory retina.

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Section: Discussionsupporting

confidence: 76%

Effect of flaxseed on choroid–sclera complex thickness and on LDL oxidation in the sclera, choroid and retina of diet-induced hypercholesterolaemic rabbits

Torres

Luchini²,

Both

et al. 2014

Br J Nutr

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“…In a recent study, our group showed that olmesartan reduced the expression of MCP-1 and the accumulation of macrophages in the sclera and choroid of hypercholesterolemic rabbits 31. Besides blocking the binding of angiotensin II to the AT1 receptors, olmesartan exerts a mild modulatory activity on PPAR-gamma receptors 32.…”

Section: Discussionmentioning

confidence: 97%

Effect of candesartan on the expression of sclera-choroidal intercellular adhesion molecule-1 in hypercholesterolemic models

Luchini¹,

Torres

Oliveira³

et al. 2014

Clinics

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OBJECTIVE:To evaluate the effect of blocking the angiotensin II AT-1 receptor by the systemic administration of candesartan on the expression of intercellular adhesion molecule-1 in the sclera and choroid of hypercholesterolemic rabbits.METHODS:New Zealand rabbits were divided into 3 groups, as follows: GI, which was fed a rabbit standard diet; GII, which was fed a hypercholesterolemic diet; and GIII, which received hypercholesterolemic diet plus candesartan. Samples of the rabbits' sclera and choroid were then studied by hematoxylin-eosin staining and histomorphometric and immunohistochemical analyses for intercellular adhesion molecule-1 expression.RESULTS:Histological analysis of hematoxylin- and eosin-stained sclera and choroid revealed that macrophages were rarely present in GI, and GII had significantly increased macrophage numbers compared to GIII. Moreover, in GII, the sclera and choroid morphometry showed a significant increase in thickness in comparison to GI and GIII. GIII presented a significant increase in thickness in relation to GI. Sclera and choroid immunohistochemical analysis for intercellular adhesion molecule-1 expression revealed a significant increase in immunoreactivity in GII in relation to GI and GIII. GIII showed a significant increase in immunoreactivity in relation to GI.CONCLUSION:Candesartan reduced the expression of intercellular adhesion molecule-1 and consequently macrophage accumulation in the sclera and choroid of hypercholesterolemic rabbits.

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“…This short period has been proven to be sufficient to demonstrate that the serum total cholesterol, triglycerides, HDL cholesterol, and fasting glucose level remained stable and did not interfere with the immunohistochemical analysis of the choroid and sclera. The decision to euthanize rabbits of the NG group after 4 weeks was made based on the results of earlier studies (24,35) . We have demonstrated that cholesterol-enriched diet induces an increase in macrophage concentration in the choroid-sclera com plex, causing thickness of these structures (24,25,35) .…”

Section: Discussionmentioning

confidence: 99%

“…The decision to euthanize rabbits of the NG group after 4 weeks was made based on the results of earlier studies (24,35) . We have demonstrated that cholesterol-enriched diet induces an increase in macrophage concentration in the choroid-sclera com plex, causing thickness of these structures (24,25,35) . The diet also induced hypoxia of the retinal tissue, leading to neuronal damage (35) .…”

Section: Discussionmentioning

confidence: 99%

“…We have demonstrated that cholesterol-enriched diet induces an increase in macrophage concentration in the choroid-sclera com plex, causing thickness of these structures (24,25,35) . The diet also induced hypoxia of the retinal tissue, leading to neuronal damage (35) . Therefore, the hypercholesterolemic model used in the present study incorporates the increased macrophage concentration and hypoxia, the two conditions that induce TNF-α and IL-6 expression (19,22,24) .…”

Section: Discussionmentioning

confidence: 99%

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Expression of TNF-α and IL-6 cytokines in the choroid and sclera of hypercholesterolemic rabbits

Torres

Luchini²,

Barberini

et al. 2014

Arquivos Brasileiros De Oftalmologia

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Effect of Olmesartan on Leukocyte Recruitment in Choroid–Sclera Complex in Hypercholesterolemia Model

Abstract: Olmesartan reduced the MCP-1 expression and the resultant macrophage accumulation in the choroid-sclera complex of hypercholesterolemic rabbits.

Cited by 5 publications

References 35 publications

Effect of flaxseed on choroid–sclera complex thickness and on LDL oxidation in the sclera, choroid and retina of diet-induced hypercholesterolaemic rabbits

Effect of flaxseed on choroid–sclera complex thickness and on LDL oxidation in the sclera, choroid and retina of diet-induced hypercholesterolaemic rabbits

Effect of candesartan on the expression of sclera-choroidal intercellular adhesion molecule-1 in hypercholesterolemic models

Expression of TNF-α and IL-6 cytokines in the choroid and sclera of hypercholesterolemic rabbits

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