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Chemokine Mediated Monocyte Trafficking into the Retina: Role of Inflammation in Alteration of the Blood-Retinal Barrier in Diabetic Retinopathy
Open accessAbstract
Inflammation in the diabetic retina is mediated by leukocyte adhesion to the retinal vasculature and alteration of the blood-retinal barrier (BRB). We investigated the role of chemokines in the alteration of the BRB in diabetes. Animals were made diabetic by streptozotocin injection and analyzed for gene expression and monocyte/macrophage infiltration. The expression of CCL2 (chemokine ligand 2) was significantly up-regulated in the retinas of rats with 4 and 8 weeks of diabetes and also in human retinal endothelial cells treated with high glucose and glucose flux. Additionally, diabetes or intraocular injection of recombinant CCL2 resulted in increased expression of the macrophage marker, F4/80. Cell culture impedance sensing studies showed that purified CCL2 was unable to alter the integrity of the human retinal endothelial cell barrier, whereas monocyte conditioned medium resulted in significant reduction in cell resistance, suggesting the relevance of CCL2 in early immune cell recruitment for subsequent barrier alterations. Further, using Cx3cr1-GFP mice, we found that intraocular injection of CCL2 increased retinal GFP+ monocyte/macrophage infiltration. When these mice were made diabetic, increased infiltration of monocytes/macrophages was also present in retinal tissues. Diabetes and CCL2 injection also induced activation of retinal microglia in these animals. Quantification by flow cytometry demonstrated a two-fold increase of CX3CR1+/CD11b+ (monocyte/macrophage and microglia) cells in retinas of wildtype diabetic animals in comparison to control non-diabetic ones. Using CCL2 knockout (Ccl2-/-) mice, we show a significant reduction in retinal vascular leakage and monocyte infiltration following induction of diabetes indicating the importance of this chemokine in alteration of the BRB. Thus, CCL2 may be an important therapeutic target for the treatment of diabetic macular edema.
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Cites
CCR3 is a target for age-related macular degeneration diagnosis and therapy
Takeda, A., Baffi, J. Z., Kleinman, M. E., Cho, W. G., Nozaki, M., Yamada, K., Kaneko, H., Albuquerque, R. J. C., Dridi, S., Saito, K., et al. (2009) · Nature · doi:10.1038/nature08151 · Cited by 263
Effects of the Chemokine CCL2 on Blood–Brain Barrier Permeability during Ischemia–Reperfusion Injury
Dimitrijevic, O. B., Stamatovic, S. M., Keep, R. F., & Andjelkovic, A. V. (2006) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600229 · Cited by 252
Cited by
Tan, G. S., Cheung, N., Simó, R., Cheung, G. C. M., & Wong, T. Y. (2017) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(16)30052-3 · Cited by 361
Macrophages: An Inflammatory Link Between Angiogenesis and Lymphangiogenesis
Corliss, B. A., Azimi, M. S., Munson, J. M., Peirce, S. M., & Murfee, W. L. (2016) · Microcirculation · doi:10.1111/micc.12259 · Cited by 356
Innate Immune Response in Retinal Homeostasis and Inflammatory Disorders
Murakami, Y., Ishikawa, K., Nakao, S., & Sonoda, K.-H. (2020) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2019.100778 · Cited by 125
Liu, W., Tzeng, T.-F., & Liu, I.-M. (2016) · Molecules · doi:10.3390/molecules21121708 · Cited by 30
Metadata
- Authors
- Rangasamy, S., McGuire, P. G., Franco Nitta, C., Monickaraj, F., Oruganti, S. R., & Das, A.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-10-20
- Volume
- 9
- Issue
- 10
- Pages
- e108508
- ISSN
- 1932-6203 (ISSN-L)
- OpenAlex
- W1986398399
- Cited by
- 243
- References
- 2
- FWCI
- 15.12
- Type
- journal article
- Language
- en
- Open access
- gold
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- CoChat. (2026). Citation check: Chemokine Mediated Monocyte Trafficking into the Retina: Role of Inflammation in Alteration of the Blood-Retinal Barrier in Diabetic Retinopathy. https://app.cochat.ai/papers/10.1371/journal.pone.0108508
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- Rangasamy, S., McGuire, P. G., Franco Nitta, C., Monickaraj, F., Oruganti, S. R., & Das, A. (2014). Chemokine Mediated Monocyte Trafficking into the Retina: Role of Inflammation in Alteration of the Blood-Retinal Barrier in Diabetic Retinopathy. PLoS ONE. https://doi.org/10.1371/journal.pone.0108508
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