Molecular imaging of retinal endothelial injury in diabetic animals

Purpose: Diabetic retinopathy is a leading cause of vision loss. There is a great need for early diagnosis prior to the occurrence of irreversible structural damages. Expression of endothelial adhesion molecules is observed before the onset of diabetic vascular damage; however, to date, these molecu...

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Main Authors: Sonja Frimmel, Souska Zandi, Dawei Sun, Zhongyu Zhang, Alexander Schering, Mark I Melhorn, Shintaro Nakao, Ali Hafezi-Moghadam
Format: Article
Language:English
Published: Knowledge E 2017-01-01
Series:Journal of Ophthalmic & Vision Research
Subjects:
Online Access:http://www.jovr.org/article.asp?issn=2008-322X;year=2017;volume=12;issue=2;spage=175;epage=182;aulast=Frimmel
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author Sonja Frimmel
Souska Zandi
Dawei Sun
Zhongyu Zhang
Alexander Schering
Mark I Melhorn
Shintaro Nakao
Ali Hafezi-Moghadam
author_facet Sonja Frimmel
Souska Zandi
Dawei Sun
Zhongyu Zhang
Alexander Schering
Mark I Melhorn
Shintaro Nakao
Ali Hafezi-Moghadam
author_sort Sonja Frimmel
collection DOAJ
description Purpose: Diabetic retinopathy is a leading cause of vision loss. There is a great need for early diagnosis prior to the occurrence of irreversible structural damages. Expression of endothelial adhesion molecules is observed before the onset of diabetic vascular damage; however, to date, these molecules cannot be visualized in vivo. Methods: To quantify the expression of endothelial surface molecules, we generated imaging probes that bind to ICAM-1. The α-ICAM-1 probes were characterized via flow cytometry under microfluidic conditions. Probes were systemically injected into normal and diabetic rats, and their adhesion in the retinal microvessels was visualized via confocal scanning laser ophthalmoscopy. Histology was performed to validate in vivo imaging results. Vascular pathologies were visualized using trypsin-digested retinal preparations. Results: The α-ICAM-1 probes showed significantly higher adhesion to retinal microvessels in diabetic rats than in normal controls (P < 0.01), whereas binding of control probes did not differ between the two groups. Western blotting results showed higher ICAM-1 expression in retinas of T1D animals than in normal controls. Retinal endothelial ICAM-1 expression was observed via molecular imaging before markers of structural damage, such as pericyte ghosts and acellular capillaries. Conclusion: Results indicate that molecular imaging can be used to detect subtle changes in the diabetic retina prior to the occurrence of irreversible pathology. Thus, ICAM-1 could serve as a diagnostic target in patients with diabetes. This study provides a proof of principle for non-invasive subclinical diagnosis in experimental diabetic retinopathy. Further development of this technology could improve management of diabetic complications.
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spelling doaj.art-07f4068fd4a441cd9742bec6502c4d202022-12-22T02:44:06ZengKnowledge EJournal of Ophthalmic & Vision Research2008-322X2017-01-0112217518210.4103/jovr.jovr_243_16Molecular imaging of retinal endothelial injury in diabetic animalsSonja FrimmelSouska ZandiDawei SunZhongyu ZhangAlexander ScheringMark I MelhornShintaro NakaoAli Hafezi-MoghadamPurpose: Diabetic retinopathy is a leading cause of vision loss. There is a great need for early diagnosis prior to the occurrence of irreversible structural damages. Expression of endothelial adhesion molecules is observed before the onset of diabetic vascular damage; however, to date, these molecules cannot be visualized in vivo. Methods: To quantify the expression of endothelial surface molecules, we generated imaging probes that bind to ICAM-1. The α-ICAM-1 probes were characterized via flow cytometry under microfluidic conditions. Probes were systemically injected into normal and diabetic rats, and their adhesion in the retinal microvessels was visualized via confocal scanning laser ophthalmoscopy. Histology was performed to validate in vivo imaging results. Vascular pathologies were visualized using trypsin-digested retinal preparations. Results: The α-ICAM-1 probes showed significantly higher adhesion to retinal microvessels in diabetic rats than in normal controls (P < 0.01), whereas binding of control probes did not differ between the two groups. Western blotting results showed higher ICAM-1 expression in retinas of T1D animals than in normal controls. Retinal endothelial ICAM-1 expression was observed via molecular imaging before markers of structural damage, such as pericyte ghosts and acellular capillaries. Conclusion: Results indicate that molecular imaging can be used to detect subtle changes in the diabetic retina prior to the occurrence of irreversible pathology. Thus, ICAM-1 could serve as a diagnostic target in patients with diabetes. This study provides a proof of principle for non-invasive subclinical diagnosis in experimental diabetic retinopathy. Further development of this technology could improve management of diabetic complications.http://www.jovr.org/article.asp?issn=2008-322X;year=2017;volume=12;issue=2;spage=175;epage=182;aulast=FrimmelBiomarkers; Diabetic Retinopathy; Early Diagnosis; ICAM-1
spellingShingle Sonja Frimmel
Souska Zandi
Dawei Sun
Zhongyu Zhang
Alexander Schering
Mark I Melhorn
Shintaro Nakao
Ali Hafezi-Moghadam
Molecular imaging of retinal endothelial injury in diabetic animals
Journal of Ophthalmic & Vision Research
Biomarkers; Diabetic Retinopathy; Early Diagnosis; ICAM-1
title Molecular imaging of retinal endothelial injury in diabetic animals
title_full Molecular imaging of retinal endothelial injury in diabetic animals
title_fullStr Molecular imaging of retinal endothelial injury in diabetic animals
title_full_unstemmed Molecular imaging of retinal endothelial injury in diabetic animals
title_short Molecular imaging of retinal endothelial injury in diabetic animals
title_sort molecular imaging of retinal endothelial injury in diabetic animals
topic Biomarkers; Diabetic Retinopathy; Early Diagnosis; ICAM-1
url http://www.jovr.org/article.asp?issn=2008-322X;year=2017;volume=12;issue=2;spage=175;epage=182;aulast=Frimmel
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