Advanced Glycation End Products Induce Blood–Retinal Barrier Dysfunction in Normoglycemic Rats

AW Stitt, T Bhaduri, Tara Moore, J Connolly, TA Gardiner, DB Archer

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

Advanced glycation end products (AGEs) have been implicated in the progressive vascular dysfunction which occurs during diabetic retinopathy. In the current study we have examined the role of these adducts in blood–retinal barrier (BRB) breakdown and investigated expression of the vasopermeabilizing agent vascular endothelial growth factor (VEGF) in the retina. When normoglycemic rats were injected with AGE-modified albumin daily for up to 10 days there was widespread leakage of FITC-dextran and serum albumin from the retinal vasculature when compared to control animals treated with nonmodified albumin. Ultrastructural examination of the vasculature revealed areas of attenuation of the retinal vascular endothelium and increased vesicular organelles only in the AGE-exposed rats. Quantitative RT-PCR and in situ hybridization demonstrated a significant increase in retinal VEGF mRNA expression (P <0.05). These results suggest that AGEs can initiate BRB dysfunction in nondiabetic rats and a concomitant increase in retinal VEGF expression. These findings may have implications for the role of AGEs in the pathogenesis of diabetic retinopathy. Author Keywords: vascular endothelial growth factor; retina; diabetic retinopathy; advanced glycation end products; blood–retinal barrier
LanguageEnglish
JournalMolecular Cell Biology Research Communications
Volume3
DOIs
Publication statusPublished - Jun 2000

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Blood-Retinal Barrier
Advanced Glycosylation End Products
Vascular Endothelial Growth Factor A
Diabetic Retinopathy
Retina
Albumins
Retinal Vessels
Vascular Endothelium
Serum Albumin
Organelles
In Situ Hybridization
Blood Vessels
Polymerase Chain Reaction
Messenger RNA

Cite this

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title = "Advanced Glycation End Products Induce Blood–Retinal Barrier Dysfunction in Normoglycemic Rats",
abstract = "Advanced glycation end products (AGEs) have been implicated in the progressive vascular dysfunction which occurs during diabetic retinopathy. In the current study we have examined the role of these adducts in blood–retinal barrier (BRB) breakdown and investigated expression of the vasopermeabilizing agent vascular endothelial growth factor (VEGF) in the retina. When normoglycemic rats were injected with AGE-modified albumin daily for up to 10 days there was widespread leakage of FITC-dextran and serum albumin from the retinal vasculature when compared to control animals treated with nonmodified albumin. Ultrastructural examination of the vasculature revealed areas of attenuation of the retinal vascular endothelium and increased vesicular organelles only in the AGE-exposed rats. Quantitative RT-PCR and in situ hybridization demonstrated a significant increase in retinal VEGF mRNA expression (P <0.05). These results suggest that AGEs can initiate BRB dysfunction in nondiabetic rats and a concomitant increase in retinal VEGF expression. These findings may have implications for the role of AGEs in the pathogenesis of diabetic retinopathy. Author Keywords: vascular endothelial growth factor; retina; diabetic retinopathy; advanced glycation end products; blood–retinal barrier",
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Advanced Glycation End Products Induce Blood–Retinal Barrier Dysfunction in Normoglycemic Rats. / Stitt, AW; Bhaduri, T; Moore, Tara; Connolly, J; Gardiner, TA; Archer, DB.

In: Molecular Cell Biology Research Communications, Vol. 3, 06.2000.

Research output: Contribution to journalArticle

TY - JOUR

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AU - Stitt, AW

AU - Bhaduri, T

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AU - Connolly, J

AU - Gardiner, TA

AU - Archer, DB

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AB - Advanced glycation end products (AGEs) have been implicated in the progressive vascular dysfunction which occurs during diabetic retinopathy. In the current study we have examined the role of these adducts in blood–retinal barrier (BRB) breakdown and investigated expression of the vasopermeabilizing agent vascular endothelial growth factor (VEGF) in the retina. When normoglycemic rats were injected with AGE-modified albumin daily for up to 10 days there was widespread leakage of FITC-dextran and serum albumin from the retinal vasculature when compared to control animals treated with nonmodified albumin. Ultrastructural examination of the vasculature revealed areas of attenuation of the retinal vascular endothelium and increased vesicular organelles only in the AGE-exposed rats. Quantitative RT-PCR and in situ hybridization demonstrated a significant increase in retinal VEGF mRNA expression (P <0.05). These results suggest that AGEs can initiate BRB dysfunction in nondiabetic rats and a concomitant increase in retinal VEGF expression. These findings may have implications for the role of AGEs in the pathogenesis of diabetic retinopathy. Author Keywords: vascular endothelial growth factor; retina; diabetic retinopathy; advanced glycation end products; blood–retinal barrier

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