Defibrinogenation Ameliorates Retinal Microgliosis and Inflammation in A CX3CR1-Independent Manner

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dc.contributor.authorSarker, Borna
dc.contributor.authorCardona, Sandra M.
dc.contributor.authorChurch, Kaira A.
dc.contributor.authorVanegas, Difernando
dc.contributor.authorVelazquez, Priscila
dc.contributor.authorRorex, Colin
dc.contributor.authorRodriguez, Derek
dc.contributor.authorMendiola, Andrew S.
dc.contributor.authorKern, Timothy S.
dc.contributor.authorDomingo, Nadia D.
dc.contributor.authorStephens, Robin
dc.contributor.authorMuzzio, Isabel A.
dc.contributor.authorCardona, Astrid E.
dc.creator.orcidhttps://orcid.org/0000-0002-5093-8078en_US
dc.date.accessioned2023-05-11T15:41:34Z
dc.date.available2023-05-11T15:41:34Z
dc.date.issued2022-10-11
dc.description.abstractMicroglia-mediated inflammation plays a significant role in neuronal and vascular damage in diabetic retinopathy (DR), but the mechanism linking inflammation, neurodegeneration, and impaired vascular integrity is still unclear. Previous studies from diabetic mouse models showed accumulation of fibrinogen at vessel lesions surrounded by perivascular microglial clusters. The purpose of this study was to evaluate whether the pathological hallmarks of gliosis and vascular aberrations characterized in diabetic animal models are consistent with those in diabetic human retinas, and to assess the effects of the defibrinogenating agent ancrod in retinal pathology and visual acuity in a two-hit inflammatory diabetic mouse model. Post-mortem human eyes were assessed for retinal and inflammatory gene expression by quantitative PCR. Immunohistochemical analyses in human and murine retinas were performed using markers of gliosis, vascular integrity, and fibrinogen deposition. An inflammatory microenvironment, with microgliosis and microaneurysms, was found in the diabetic human eye. Microglial activation, fibrinogen deposition, and axonal loss were also observed in the diabetic murine retina. Ancrod treatment correlated with reduced microgliosis, less fibrinogen deposition, and reduced pro-inflammatory cytokine levels in diseased retinal tissues. Together, these data suggest that fibrinogen contributes to microglia-mediated inflammation in the diabetic retina. Since retinal microgliosis, vascular pathology, and vision deficits manifest in diabetic mice irrespective of CX3CR1 genotype, our results indicate that defibrinogenation can dampen systemic neuroinflammation and vascular insults, thereby improving vision at early stages of diabetes.en_US
dc.description.departmentMolecular Microbiology and Immunologyen_US
dc.description.sponsorshipNational Institutes of Health; University of Texas at San Antonio; National Science Foundationen_US
dc.identifier.citationSarker, B., Cardona, S. M., Church, K. A., Vanegas, D., Velazquez, P., Rorex, C., . . . Cardona, A. E. (2022). Defibrinogenation Ameliorates Retinal Microgliosis and Inflammation in A CX3CR1-Independent Manner. ASN Neuro, 14. doi:10.1177/17590914221131446en_US
dc.identifier.issn1759-9091
dc.identifier.otherhttps://doi.org/10.1177/17590914221131446
dc.identifier.urihttps://hdl.handle.net/20.500.12588/1832
dc.language.isoen_USen_US
dc.publisherSAGE Publicationsen_US
dc.rightsAttribution-NonCommercial 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/us/*
dc.subjectmicrogliaen_US
dc.subjectdiabetic retinopathyen_US
dc.subjectfibrinogenen_US
dc.subjectinflammationen_US
dc.subjectancroden_US
dc.subjectvisual acuityen_US
dc.titleDefibrinogenation Ameliorates Retinal Microgliosis and Inflammation in A CX3CR1-Independent Manneren_US
dc.typeArticleen_US

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