Tags

Type your tag names separated by a space and hit enter

Age-related macular degeneration phenotypes are associated with increased tumor necrosis-alpha and subretinal immune cells in aged Cxcr5 knockout mice.
PLoS One. 2017; 12(3):e0173716.Plos

Abstract

The role of chemokine receptor in age-related macular degeneration (AMD) remains elusive. The objective of this study is to investigate the role of chemokine receptor Cxcr5 in the pathogenesis of AMD. Cxcr5 gene expression levels (mRNA and protein) are higher in the retina and retinal pigment epithelium (RPE) of aged C57BL/6 wild type mice than younger ones. Vascular and glial cells express Cxcr5 and its ligand Cxcl13 in mouse retina. Aged Cxcr5 knockout (-/-) mice develop both early and late AMD-like pathological features. White and yellow spots, which look like drusen in humans, were identified with fundscopic examination. Drusen-like sub-RPE deposits with dome-shaped morphology were characterized on the sections. RPE vacuolization, swelling, and sub-RPE basal deposits were illustrated with light and transmission electron microscope (TEM). TEM further illustrated degenerated and disorganized RPE basal infoldings, phagosomes and melanosomes inside RPE, as well as abnormal photoreceptor outer segments. Lipofuscin granules and lipid droplets in the subretinal space, RPE, and choroid were revealed with fluorescence microscope and oil-red-O staining. Increased IgG in RPE/choroid were determined with Western blots (WB). WB and immunofluorescence staining determined RPE zona occuldens (ZO)-1 protein reduction and abnormal subcellular localization. TUNEL staining, outer nuclear layer (ONL) measurement and electroretinogram (ERG) recording indicated that photoreceptors underwent apoptosis, degeneration, and functional impairment. Additionally, spontaneous neovascularization (NV)-like lesions develop in the subretinal space of aged Cxcr5-/- mice. The underlying mechanisms are associated with increased subretinal F4/80+ immune cells, some of which contain RPE marker RPE65, and up-regulation of the multifunctional cytokine tumor necrosis factor-alpha (TNF-α) in RPE/choroid and retina. These findings suggest that Cxcr5 itself may be involved in the protection of RPE and retinal cells during aging and its loss may lead to AMD-like pathological changes in aged mice.

Authors+Show Affiliations

The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America. Aier Eye Hospital of Changsha, Hunan, China.The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America. School of Ophthalmology, Central South University, Changsha, Hunan, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28282423

Citation

Huang, Hu, et al. "Age-related Macular Degeneration Phenotypes Are Associated With Increased Tumor Necrosis-alpha and Subretinal Immune Cells in Aged Cxcr5 Knockout Mice." PloS One, vol. 12, no. 3, 2017, pp. e0173716.
Huang H, Liu Y, Wang L, et al. Age-related macular degeneration phenotypes are associated with increased tumor necrosis-alpha and subretinal immune cells in aged Cxcr5 knockout mice. PLoS One. 2017;12(3):e0173716.
Huang, H., Liu, Y., Wang, L., & Li, W. (2017). Age-related macular degeneration phenotypes are associated with increased tumor necrosis-alpha and subretinal immune cells in aged Cxcr5 knockout mice. PloS One, 12(3), e0173716. https://doi.org/10.1371/journal.pone.0173716
Huang H, et al. Age-related Macular Degeneration Phenotypes Are Associated With Increased Tumor Necrosis-alpha and Subretinal Immune Cells in Aged Cxcr5 Knockout Mice. PLoS One. 2017;12(3):e0173716. PubMed PMID: 28282423.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Age-related macular degeneration phenotypes are associated with increased tumor necrosis-alpha and subretinal immune cells in aged Cxcr5 knockout mice. AU - Huang,Hu, AU - Liu,Ying, AU - Wang,Lei, AU - Li,Wen, Y1 - 2017/03/10/ PY - 2016/09/06/received PY - 2017/02/24/accepted PY - 2017/3/11/entrez PY - 2017/3/11/pubmed PY - 2017/8/18/medline SP - e0173716 EP - e0173716 JF - PloS one JO - PLoS One VL - 12 IS - 3 N2 - The role of chemokine receptor in age-related macular degeneration (AMD) remains elusive. The objective of this study is to investigate the role of chemokine receptor Cxcr5 in the pathogenesis of AMD. Cxcr5 gene expression levels (mRNA and protein) are higher in the retina and retinal pigment epithelium (RPE) of aged C57BL/6 wild type mice than younger ones. Vascular and glial cells express Cxcr5 and its ligand Cxcl13 in mouse retina. Aged Cxcr5 knockout (-/-) mice develop both early and late AMD-like pathological features. White and yellow spots, which look like drusen in humans, were identified with fundscopic examination. Drusen-like sub-RPE deposits with dome-shaped morphology were characterized on the sections. RPE vacuolization, swelling, and sub-RPE basal deposits were illustrated with light and transmission electron microscope (TEM). TEM further illustrated degenerated and disorganized RPE basal infoldings, phagosomes and melanosomes inside RPE, as well as abnormal photoreceptor outer segments. Lipofuscin granules and lipid droplets in the subretinal space, RPE, and choroid were revealed with fluorescence microscope and oil-red-O staining. Increased IgG in RPE/choroid were determined with Western blots (WB). WB and immunofluorescence staining determined RPE zona occuldens (ZO)-1 protein reduction and abnormal subcellular localization. TUNEL staining, outer nuclear layer (ONL) measurement and electroretinogram (ERG) recording indicated that photoreceptors underwent apoptosis, degeneration, and functional impairment. Additionally, spontaneous neovascularization (NV)-like lesions develop in the subretinal space of aged Cxcr5-/- mice. The underlying mechanisms are associated with increased subretinal F4/80+ immune cells, some of which contain RPE marker RPE65, and up-regulation of the multifunctional cytokine tumor necrosis factor-alpha (TNF-α) in RPE/choroid and retina. These findings suggest that Cxcr5 itself may be involved in the protection of RPE and retinal cells during aging and its loss may lead to AMD-like pathological changes in aged mice. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/28282423/Age_related_macular_degeneration_phenotypes_are_associated_with_increased_tumor_necrosis_alpha_and_subretinal_immune_cells_in_aged_Cxcr5_knockout_mice_ L2 - https://dx.plos.org/10.1371/journal.pone.0173716 DB - PRIME DP - Unbound Medicine ER -