N-3 Polyunsaturated Fatty Acids Prevent Diabetic Retinopathy by Inhibition of Retinal Vascular Damage and Enhanced Endothelial Progenitor Cell Reparative Function
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{"title"=>"N-3 Polyunsaturated Fatty Acids Prevent Diabetic Retinopathy by Inhibition of Retinal Vascular Damage and Enhanced Endothelial Progenitor Cell Reparative Function", "type"=>"journal", "authors"=>[{"first_name"=>"Maria", "last_name"=>"Tikhonenko", "scopus_author_id"=>"36978696700"}, {"first_name"=>"Todd A.", "last_name"=>"Lydic", "scopus_author_id"=>"6506197249"}, {"first_name"=>"Madalina", "last_name"=>"Opreanu", "scopus_author_id"=>"25927983200"}, {"first_name"=>"Sergio", "last_name"=>"Li Calzi", "scopus_author_id"=>"14056098300"}, {"first_name"=>"Svetlana", "last_name"=>"Bozack", "scopus_author_id"=>"54388643700"}, {"first_name"=>"Kelly M.", "last_name"=>"McSorley", "scopus_author_id"=>"6506565059"}, {"first_name"=>"Andrew L.", "last_name"=>"Sochacki", "scopus_author_id"=>"35300877900"}, {"first_name"=>"Matthew S.", "last_name"=>"Faber", "scopus_author_id"=>"55337065500"}, {"first_name"=>"Sugata", "last_name"=>"Hazra", "scopus_author_id"=>"55498654100"}, {"first_name"=>"Shane", "last_name"=>"Duclos", "scopus_author_id"=>"55519992400"}, {"first_name"=>"Dennis", "last_name"=>"Guberski", "scopus_author_id"=>"6603346408"}, {"first_name"=>"Gavin E.", "last_name"=>"Reid", "scopus_author_id"=>"7402424649"}, {"first_name"=>"Maria B.", "last_name"=>"Grant", "scopus_author_id"=>"7401439724"}, {"first_name"=>"Julia V.", "last_name"=>"Busik", "scopus_author_id"=>"6602595151"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84873833204", "sgr"=>"84873833204", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0055177", "pmid"=>"23383097", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pui"=>"368226692"}, "id"=>"bc017db9-38b4-3f8f-920e-d461dd96b826", "abstract"=>"OBJECTIVE: The vasodegenerative phase of diabetic retinopathy is characterized by not only retinal vascular degeneration but also inadequate vascular repair due to compromised bone marrow derived endothelial progenitor cells (EPCs). We propose that n-3 polyunsaturated fatty acid (PUFA) deficiency in diabetes results in activation of the central enzyme of sphingolipid metabolism, acid sphingomyelinase (ASM) and that ASM represents a molecular metabolic link connecting the initial damage in the retina and the dysfunction of EPCs.\\n\\nRESEARCH DESIGN AND METHODS: Type 2 diabetic rats on control or docosahexaenoic acid (DHA)-rich diet were studied. The number of acellular capillaries in the retinas was assessed by trypsin digest. mRNA levels of interleukin (IL)-1β, IL-6, intracellular adhesion molecule (ICAM)-1 in the retinas from diabetic animals were compared to controls and ASM protein was assessed by western analysis. EPCs were isolated from blood and bone marrow and their numbers and ability to form colonies in vitro, ASM activity and lipid profiles were determined.\\n\\nRESULTS: DHA-rich diet prevented diabetes-induced increase in the number of retinal acellular capillaries and significantly enhanced the life span of type 2 diabetic animals. DHA-rich diet blocked upregulation of ASM and other inflammatory markers in diabetic retina and prevented the increase in ASM activity in EPCs, normalized the numbers of circulating EPCs and improved EPC colony formation.\\n\\nCONCLUSIONS: In a type 2 diabetes animal model, DHA-rich diet fully prevented retinal vascular pathology through inhibition of ASM in both retina and EPCs, leading to a concomitant suppression of retinal inflammation and correction of EPC number and function.", "link"=>"http://www.mendeley.com/research/n3-polyunsaturated-fatty-acids-prevent-diabetic-retinopathy-inhibition-retinal-vascular-damage-enhan", "reader_count"=>31, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>3, "Librarian"=>1, "Student > Doctoral Student"=>2, "Researcher"=>5, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>1, "Student > Master"=>5, "Other"=>1, "Student > Bachelor"=>3, "Lecturer"=>3, "Professor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>3, "Librarian"=>1, "Student > Doctoral Student"=>2, "Researcher"=>5, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>1, "Student > Master"=>5, "Other"=>1, "Student > Bachelor"=>3, "Lecturer"=>3, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Nursing and Health Professions"=>1, "Medicine and Dentistry"=>11, "Agricultural and Biological Sciences"=>12, "Neuroscience"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Social Sciences"=>1, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>11}, "Neuroscience"=>{"Neuroscience"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>12}, "Computer Science"=>{"Computer Science"=>1}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Japan"=>2, "Italy"=>2, "Australia"=>1, "Portugal"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/500366"], "description"=>"<p>A) Trypsin digests of rat retinas stained with hematoxylin and periodic acid–Schiff. Representative regions around the mid-retina used for counting are shown. Bars,10 µM. Significantly increased number of acellular capillaries (black arrows) was observed in retinal vasculature isolated from diabetic animals compared with control. No significant difference was found between diabetic animals fed DHA diet and control animals. (B) Quantification of acellular capillaries in n = 9 in control and diabetes soybean diet group, n = 4 in diabetes DHA diet group. *** = p<0.001 compared to control animals group and <sup>###</sup> = p<0.001 compared to diabetic animals fed with soybean oil diet.</p>", "links"=>[], "tags"=>["prevents", "acellular", "capillaries"], "article_id"=>170852, "categories"=>["Chemistry", "Immunology", "Medicine"], "users"=>["Maria Tikhonenko", "Todd A. Lydic", "Madalina Opreanu", "Sergio Li Calzi", "Svetlana Bozack", "Kelly M. McSorley", "Andrew L. Sochacki", "Matthew S. Faber", "Sugata Hazra", "Shane Duclos", "Dennis Guberski", "Gavin E. Reid", "Maria B. Grant", "Julia V. Busik"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055177.g001", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DHA_enriched_fish_oil_diet_prevents_the_formation_of_acellular_capillaries_in_type_2_diabetes_model_/170852", "title"=>"DHA-enriched fish oil diet prevents the formation of acellular capillaries in type 2 diabetes model.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 16:25:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/501469"], "description"=>"<p>Clinical characteristics of control and diabetic patients involved in the study.</p>", "links"=>[], "tags"=>["characteristics", "diabetic", "patients"], "article_id"=>171975, "categories"=>["Chemistry", "Immunology", "Medicine"], "users"=>["Maria Tikhonenko", "Todd A. Lydic", "Madalina Opreanu", "Sergio Li Calzi", "Svetlana Bozack", "Kelly M. McSorley", "Andrew L. Sochacki", "Matthew S. Faber", "Sugata Hazra", "Shane Duclos", "Dennis Guberski", "Gavin E. Reid", "Maria B. Grant", "Julia V. Busik"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055177.t002", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_characteristics_of_control_and_diabetic_patients_involved_in_the_study_/171975", "title"=>"Clinical characteristics of control and diabetic patients involved in the study.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-19 16:31:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/500738"], "description"=>"<p>A) EPCs were extracted by magnetic beads method from total peripheral blood. After 2 months of diabetes and feeding of the experimental diet, control and diabetic animals fed soybean or fish oil diet were used and the number of circulating EPCs. n = 8 controls, n = 5 in diabetes soybean oil diet, n = 7 in diabetes fish oil diet. * = p<0.05 compared to control animals group, <sup>#</sup> = p<0.05 compared to diabetic animals fed with soybean oil diet. B) EPCs were extracted by magnetic beads method from bone marrow and analyzed by colony formation assay. EPC colony formation was significantly decreased in diabetic rats compared to controls but corrected by DHA-enriched fish oil diet. The images of the colonies from control and diabetic animals are shown above the respective graphs. n = 4 in each group. * = p<0.05, ** = p<0.01 compared to control animals group, <sup>###</sup> = p<0.001 compared to diabetic animals fed with soybean oil diet.</p>", "links"=>[], "tags"=>["normalizes", "circulating", "marrow", "epc", "numbers"], "article_id"=>171240, "categories"=>["Chemistry", "Immunology", "Medicine"], "users"=>["Maria Tikhonenko", "Todd A. Lydic", "Madalina Opreanu", "Sergio Li Calzi", "Svetlana Bozack", "Kelly M. McSorley", "Andrew L. Sochacki", "Matthew S. Faber", "Sugata Hazra", "Shane Duclos", "Dennis Guberski", "Gavin E. Reid", "Maria B. Grant", "Julia V. Busik"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055177.g004", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DHA_enriched_fish_oil_diet_normalizes_circulating_and_bone_marrow_EPC_numbers_in_type_2_diabetes_model_/171240", "title"=>"DHA-enriched fish oil diet normalizes circulating and bone marrow EPC numbers in type 2 diabetes model.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 16:27:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/501146"], "description"=>"<p>EPCs were extracted by magnetic beads method from blood of diabetic patients. Cells were pre-treated with BSA vehicle (untreated) or 100 µM DHA and then placed in Boyden chamber for migration assay. Migration towards FBS was used as positive control. n = 4 in each group. ** = p<0.01 compared to positive control group, <sup>###</sup> = p<0.001 compared to untreated diabetic group.</p>", "links"=>[], "tags"=>["dha", "pretreatment", "improves"], "article_id"=>171655, "categories"=>["Chemistry", "Immunology", "Medicine"], "users"=>["Maria Tikhonenko", "Todd A. Lydic", "Madalina Opreanu", "Sergio Li Calzi", "Svetlana Bozack", "Kelly M. McSorley", "Andrew L. Sochacki", "Matthew S. Faber", "Sugata Hazra", "Shane Duclos", "Dennis Guberski", "Gavin E. Reid", "Maria B. Grant", "Julia V. Busik"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055177.g007", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_vitro_DHA_pretreatment_improves_human_CD34_cell_migration_/171655", "title"=>"In <i>vitro</i> DHA pretreatment improves human CD34<sup>+</sup> cell migration.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 16:29:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/500843"], "description"=>"<p>Diabetic bone marrow EPC showed a significant increase in ASM activity. However, the EPCs derived from diabetic animals fed DHA-rich fish oil diet showed reduced ASM activity that was similar to that observed in control rats. n = 8 controls, n = 3 in diabetes soybean oil diet, n = 5 in diabetes fish oil diet. *** = p<0.001 compared to control animals group and <sup>###</sup> = p<0.001 compared to diabetic animals fed with soybean oil diet.</p>", "links"=>[], "tags"=>["asm", "observed", "diabetic", "epcs", "prevented", "dha-rich"], "article_id"=>171343, "categories"=>["Chemistry", "Immunology", "Medicine"], "users"=>["Maria Tikhonenko", "Todd A. Lydic", "Madalina Opreanu", "Sergio Li Calzi", "Svetlana Bozack", "Kelly M. McSorley", "Andrew L. Sochacki", "Matthew S. Faber", "Sugata Hazra", "Shane Duclos", "Dennis Guberski", "Gavin E. Reid", "Maria B. Grant", "Julia V. Busik"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055177.g005", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_increase_in_ASM_activity_observed_in_diabetic_EPCs_is_prevented_by_DHA_rich_fish_oil_diet_/171343", "title"=>"The increase in ASM activity observed in diabetic EPCs is prevented by DHA-rich fish oil diet.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 16:27:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/501285"], "description"=>"<p>After induction of diabetes, rats were randomly assigned to soybean (black line) or DHA-rich fish oil diet (gray line) shown as day 0. Control animals (dashed line) were fed soybean oil diet. Survival was then assessed for 190 days. Diabetic rats fed DHA-rich fish oil diet had statistically improved survival as compared to soybean oil diet. n = 45 of control animals group, n = 45 of diabetic animals fed soybean oil group, n = 25 of diabetic animals fed fish oil group. *** = p<0.001 compared to control animals group and <sup>###</sup> = p<0.001 compared to diabetic animals fed with soybean oil diet.</p>", "links"=>[], "tags"=>["improves", "span", "diabetic"], "article_id"=>171792, "categories"=>["Chemistry", "Immunology", "Medicine"], "users"=>["Maria Tikhonenko", "Todd A. Lydic", "Madalina Opreanu", "Sergio Li Calzi", "Svetlana Bozack", "Kelly M. McSorley", "Andrew L. Sochacki", "Matthew S. Faber", "Sugata Hazra", "Shane Duclos", "Dennis Guberski", "Gavin E. Reid", "Maria B. Grant", "Julia V. Busik"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055177.g008", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DHA_rich_fish_oil_diet_improves_life_span_in_type_2_diabetic_rats_/171792", "title"=>"DHA-rich fish oil diet improves life span in type 2 diabetic rats.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 16:30:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/500602"], "description"=>"<p>(A) Retinal acid sphingomyelinase protein levels were assessed by Western blot analysis. (B) Quantification of 4 rats/condition is shown in and normalized by tubulin (loading control). *** = p<0.001 compared to control animals group and <sup>###</sup> = p<0.001 compared to diabetic animals fed with soybean oil diet.</p>", "links"=>[], "tags"=>["normalizes", "asm", "levels", "retinas", "diabetic"], "article_id"=>171112, "categories"=>["Chemistry", "Immunology", "Medicine"], "users"=>["Maria Tikhonenko", "Todd A. Lydic", "Madalina Opreanu", "Sergio Li Calzi", "Svetlana Bozack", "Kelly M. McSorley", "Andrew L. Sochacki", "Matthew S. Faber", "Sugata Hazra", "Shane Duclos", "Dennis Guberski", "Gavin E. Reid", "Maria B. Grant", "Julia V. Busik"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055177.g003", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DHA_enriched_fish_oil_diet_normalizes_the_ASM_protein_levels_in_the_whole_retinas_of_type_2_diabetic_rats_/171112", "title"=>"DHA-enriched fish oil diet normalizes the ASM protein levels in the whole retinas of type 2 diabetic rats.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 16:26:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/501014"], "description"=>"<p>Bacterial sphingomyelinase was incubated with d18:1/12:0, d18:1/16:0, d18:1/18:0, d18:1/24:0 and d18:1/24:1 sphingomyelin and fluorescence was measured as an indicator of the enzyme specificity towards each substrate. One-way ANOVA demonstrated significant difference between specificity towards different saturated fatty acid-containing SM. p<0.001, n = 3 for each substrate. The power-fit trendline was plotted for Sphingomyelin with unsaturated acyl chain. The accuracy of the curve is more that 95% for equation y = 2704.3×<sup>−0.517</sup>.</p>", "links"=>[], "tags"=>["demonstrated", "specificity", "sphingomyelin", "shorter", "fatty", "acyl"], "article_id"=>171510, "categories"=>["Chemistry", "Immunology", "Medicine"], "users"=>["Maria Tikhonenko", "Todd A. Lydic", "Madalina Opreanu", "Sergio Li Calzi", "Svetlana Bozack", "Kelly M. McSorley", "Andrew L. Sochacki", "Matthew S. Faber", "Sugata Hazra", "Shane Duclos", "Dennis Guberski", "Gavin E. Reid", "Maria B. Grant", "Julia V. Busik"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055177.g006", "stats"=>{"downloads"=>1, "page_views"=>23, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Sphingomyelinase_demonstrated_more_specificity_towards_sphingomyelin_with_shorter_fatty_acyl_chain_/171510", "title"=>"Sphingomyelinase demonstrated more specificity towards sphingomyelin with shorter fatty acyl chain.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 16:28:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/500496"], "description"=>"<p>Gene expression of pro-inflammatory and pro-angiogenic mediators was assessed by real-time qPCR using the whole retina. A significant increase in IL-1β, IL-6, TNFα and ICAM levels was observed in diabetic rats fed a standard diet compared to control rats. DHA-enriched diet prevented these levels from reaching significant increase. n = 10 controls, n = 4 diabetes soybean oil, n = 8 diabetes fish oil. Data are expressed as the mean ± SE. * = p<0.05 compared to control animals group.</p>", "links"=>[], "tags"=>["prevents", "icam"], "article_id"=>171003, "categories"=>["Chemistry", "Immunology", "Medicine"], "users"=>["Maria Tikhonenko", "Todd A. Lydic", "Madalina Opreanu", "Sergio Li Calzi", "Svetlana Bozack", "Kelly M. McSorley", "Andrew L. Sochacki", "Matthew S. Faber", "Sugata Hazra", "Shane Duclos", "Dennis Guberski", "Gavin E. Reid", "Maria B. Grant", "Julia V. Busik"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055177.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DHA_enriched_fish_oil_diet_prevents_increase_in_IL_1_946_IL_6_TNF_945_and_ICAM_gene_expression_in_type_2_diabetes_model_/171003", "title"=>"DHA-enriched fish oil diet prevents increase in IL-1β, IL-6, TNFα and ICAM gene expression in type 2 diabetes model.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 16:25:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/501517"], "description"=>"<p>Arrows pointing up indicate significant increase, arrows pointing down – significant decrease in diabetic EPCs as compared to control.</p>", "links"=>[], "tags"=>["diabetic"], "article_id"=>172029, "categories"=>["Chemistry", "Immunology", "Medicine"], "users"=>["Maria Tikhonenko", "Todd A. Lydic", "Madalina Opreanu", "Sergio Li Calzi", "Svetlana Bozack", "Kelly M. McSorley", "Andrew L. Sochacki", "Matthew S. Faber", "Sugata Hazra", "Shane Duclos", "Dennis Guberski", "Gavin E. Reid", "Maria B. Grant", "Julia V. Busik"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055177.t001", "stats"=>{"downloads"=>5, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Sphingolipids_in_control_and_diabetic_CD34_EPCs_/172029", "title"=>"Sphingolipids in control and diabetic CD34+ EPCs.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-19 16:31:20"}

PMC Usage Stats | Further Information

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Relative Metric

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