title: High-mobility group box-1 and biomarkers of inflammation in the vitreous from patients with proliferative diabetic retinopathy.
abstract: OBJECTIVE
  To measure levels of high-mobility group box -1 (HMGB1) and soluble receptor for advanced glycation end products (sRAGE) in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR) and to correlate their levels with clinical disease activity and the levels of the inflammatory biomarkers monocyte chemoattractant protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-1β (IL-1β), and granulocyte macrophage colony-stimulating factor (GM-CSF). In addition, we examined the expression of HMGB1 in the retinas of diabetic mice.
  
  
  METHODS
  Vitreous samples from 29 PDR and 17 nondiabetic patients were studied by enzyme-linked immunosorbent assay. Retinas of mice were examined by immunofluorescence analysis and western blotting.
  
  
  RESULTS
  HMGB1 was detected in all vitreous samples and sRAGE was detected in 5 PDR samples. IL-1β was detected in 3PDR samples and GM-CSF was not detected. Mean HMGB1 levels in PDR with active neovascularization were twofold and threefold higher than that in inactive PDR and nondiabetic patients, respectively. Mean HMGB1 levels in PDR patients with hemorrhage were significantly higher than those in PDR patients without hemorrhage and nondiabetic patients (p=0.0111). There were significant correlations between levels of HMGB1 and levels of MCP-1 (r=0.333, p=0.025) and sICAM-1 (r=0.548, p<0.001). HMGB1 expression was also upregulated in the retinas of diabetic mice.
  
  
  CONCLUSIONS
  Subclinical chronic inflammation might contribute to the progression of PDR.
authors.affiliation: Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia. abuasrar@KSU.edu.sa
authors.forename: Ahmed M Abu
authors.initials: AM
authors.lastname: El-Asrar
authors.forename: Mohd Imtiaz
authors.initials: MI
authors.lastname: Nawaz
authors.forename: Dustan
authors.initials: D
authors.lastname: Kangave
authors.forename: Karel
authors.initials: K
authors.lastname: Geboes
authors.forename: Mohammad Shamsul
authors.initials: MS
authors.lastname: Ola
authors.forename: Saif
authors.initials: S
authors.lastname: Ahmad
authors.forename: Mohamed
authors.initials: M
authors.lastname: Al-Shabrawey
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000032:analysis*; D015153:Blotting, Western; D018932:Chemokine CCL2 / Q000032:analysis / Q000096:biosynthesis; D048909:Diabetes Complications / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D003930:Diabetic Retinopathy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D024243:HMGB1 Protein / Q000032:analysis / Q000096:biosynthesis; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000032:analysis / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000032:analysis / Q000096:biosynthesis; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D015861:Retinal Neovascularization / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D014821:Vitrectomy; D018630:Vitreoretinopathy, Proliferative / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D014822:Vitreous Body / Q000378:metabolism* / Q000473:pathology / Q000601:surgery
chemical_list: D015415:Biomarkers; D018932:Chemokine CCL2; D024243:HMGB1 Protein; D053583:Interleukin-1beta; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D018799:Intercellular Adhesion Molecule-1