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Graefe's Archive for Clinical and Experimental Ophthalmology

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20.08.2020 | Basic Science

A potential novel therapeutic target in diabetic retinopathy: a chemokine receptor (CCR2/CCR5) inhibitor reduces retinal vascular leakage in an animal model

verfasst von: Finny Monickaraj, Sreenivasa R. Oruganti, Paul McGuire, Arup Das

Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology | Ausgabe 1/2021

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Abstract

Purpose

We have previously shown that the chemokine CCL2 plays an important role in monocyte trafficking into the retina and alteration of the BRB in an animal model of diabetic retinopathy. In this study, we examined the effect of pharmacologically targeting the chemokine pathway to reduce the increased retinal vascular permeability in this model.

Methods

C57BL/6 J mice were made diabetic using streptozotocin. After 4 months of diabetes, mice (n = 10) were treated by intraperitoneal injections of TAK-779 (dual CCR2/CCR5 inhibitor) (30 mg/kg) daily for 2 weeks. Retinal vascular permeability and protein expression were done using western blot. The SDF-1 levels were measured by ELISA. Immune cell infiltration in the retinas was measured using flow cytometry.

Results

The dual inhibitor significantly decreased retinal vascular permeability in diabetic animals. There was a significant reduction in macrophage/microglia infiltration in the retinas of treated animals. Levels of SDF-1 and ICAM-1 were significantly reduced and the tight junction protein ZO-1 level was increased, and phospho-VE-Cad was significantly reduced with drug treatment.

Conclusions

A chemokine receptor inhibitor (CCR2/CCR5) can reduce retinal vascular permeability in diabetic animals. Targeting the chemokine pathway pharmacologically may be used as a novel therapeutic strategy in management of diabetic macular edema.

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Titel: A potential novel therapeutic target in diabetic retinopathy: a chemokine receptor (CCR2/CCR5) inhibitor reduces retinal vascular leakage in an animal model
verfasst von: Finny Monickaraj
Sreenivasa R. Oruganti
Paul McGuire
Arup Das
Publikationsdatum: 20.08.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology / Ausgabe 1/2021
Print ISSN: 0721-832X
Elektronische ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-020-04884-5

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Springer Medizin

A potential novel therapeutic target in diabetic retinopathy: a chemokine receptor (CCR2/CCR5) inhibitor reduces retinal vascular leakage in an animal model

Abstract

Purpose

Methods

Results

Conclusions

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Operative Therapie und Keimnachweis bei endogener Endophthalmitis

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Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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