Document Detail


Upregulation of RAGE and its ligands in proliferative retinal disease.
MedLine Citation:
PMID:  16364297     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We sought to study the presence of the receptor for advanced glycation endproducts (RAGE) and its ligands, advanced glycation endproducts (AGEs), S100/calgranulins and amphoterin (high mobility group box 1 protein; HMGB1), in the vitreous cavity and epiretinal membranes (ERMs) of eyes of patients with proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR). Undiluted vitreous specimens were collected from 30 eyes of 30 patients undergoing pars plana vitrectomy for repair of retinal detachment (RD) secondary to PDR (n = 15) or PVR (n = 15). The vitreous samples obtained from 10 eyes undergoing macular hole repair were used as controls. Epiretinal membranes were obtained from eight eyes with PDR and from 10 eyes with PVR. The levels of AGEs in the vitreous were measured using ELISA. The vitreous levels of soluble RAGE (sRAGE), S100/calgranulins and amphoterin were measured using Western blot analyses. The localization of RAGE and its ligands in ERMs was determined with immunohistochemistry. The vitreous levels of sRAGE were significantly increased in both PDR and PVR (p < or = 0.05) compared to control vitreous. In both PDR and PVR, the vitreous levels of AGEs (p < or = 0.01), S100/calgranulins (p < or = 0.05), and amphoterin (p < or = 0.01) were also elevated compared to control eyes. Expression of RAGE was detected in six of eight ERMs from eyes with PDR and eight of 10 ERMs from eyes with PVR. Many cells expressing RAGE also expressed vimentin, suggesting a glial cell origin. Ligands for RAGE were also detected in ERMs, with AGEs detected in five eyes with PDR and eight eyes with PVR. Similarly, S100 and amphoterin ERM expression was observed in six eyes with PDR; these ligands were also expressed in ERMs from eyes with PVR (8 and 7 cases, respectively). We conclude that RAGE and its ligands are increased in the vitreous cavity of eyes with PDR and PVR and are present in ERMs of eyes with these proliferative retinal disorders. These findings suggest a role for the proinflammatory RAGE axis in the pathogenesis of proliferative retinal diseases.
Authors:
Sophia I Pachydaki; Samir R Tari; Song Eun Lee; Wanchao Ma; Joseph J Tseng; Alexander A Sosunov; Guellue Cataldergirmen; Nikolaos Scarmeas; Casper Caspersen; Stanley Chang; William M Schiff; Ann Marie Schmidt; Gaetano R Barile
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-12-20
Journal Detail:
Title:  Experimental eye research     Volume:  82     ISSN:  0014-4835     ISO Abbreviation:  Exp. Eye Res.     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-02-06     Completed Date:  2006-07-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0370707     Medline TA:  Exp Eye Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  807-15     Citation Subset:  IM    
Affiliation:
Department of Ophthalmology, College of Physician and Surgeons, Columbia University, New York, NY 10032, USA.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Aged, 80 and over
Child
Child, Preschool
Diabetic Retinopathy / metabolism*
Enzyme-Linked Immunosorbent Assay / methods
Epiretinal Membrane / metabolism
Eye Proteins / metabolism
Female
Glycosylation End Products, Advanced
HMGB1 Protein / metabolism
Humans
Leukocyte L1 Antigen Complex / metabolism
Ligands
Male
Middle Aged
Receptors, Immunologic / metabolism*
Retinal Detachment / surgery
Up-Regulation*
Vitrectomy
Vitreoretinopathy, Proliferative / metabolism*
Vitreous Body / metabolism
Chemical
Reg. No./Substance:
0/Eye Proteins; 0/Glycosylation End Products, Advanced; 0/HMGB1 Protein; 0/Leukocyte L1 Antigen Complex; 0/Ligands; 0/Receptors, Immunologic; 0/advanced glycosylation end-product receptor

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