Astrogliosis in the GFAP-CreERT2:Rosa26iDTR Mouse Model Does Not Exacerbate Retinal Microglia Activation or Müller Cell Gliosis under Hypoxic Conditions

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dc.contributor.authorRorex, Colin
dc.contributor.authorCardona, Sandra M.
dc.contributor.authorChurch, Kaira A.
dc.contributor.authorRodriguez, Derek
dc.contributor.authorVanegas, Difernando
dc.contributor.authorSaldivar, Reina
dc.contributor.authorFaz, Brianna
dc.contributor.authorCardona, Astrid E.
dc.date.accessioned2024-06-28T15:29:42Z
dc.date.available2024-06-28T15:29:42Z
dc.date.issued2024-05-10
dc.date.updated2024-06-28T15:29:43Z
dc.description.abstractDiabetic retinopathy (DR) affects over 140 million people globally. The mechanisms that lead to blindness are still enigmatic but there is evidence that sustained inflammation and hypoxia contribute to vascular damage. Despite efforts to understand the role of inflammation and microglia in DR&rsquo;s pathology, the contribution of astrocytes to hypoxic responses is less clear. To investigate the role of astrocytes in hypoxia-induced retinopathy, we utilized a 7-day systemic hypoxia model using the GFAP-Cre<sup>ERT2</sup>:Rosa26<sup>iDTR</sup> transgenic mouse line. This allows for the induction of inflammatory reactive astrogliosis following tamoxifen and diphtheria toxin administration. We hypothesize that DTx-induced astrogliosis is neuroprotective during hypoxia-induced retinopathy. Glial, neuronal, and vascular responses were quantified using immunostaining, with antibodies against GFAP, vimentin, IBA-1, NeuN, fibrinogen, and CD31. Cytokine responses were measured in both the brain and serum. We report that while both DTx and hypoxia induced a phenotype of reduced microglia morphological activation, DTx, but not hypoxia, induced an increase in the Müller glia marker vimentin. We did not observe that the combination of DTx and hypoxic treatments exacerbated the signs of reactive glial cells, nor did we observe a significant change in the expression immunomodulatory mediators IL-1&beta;, IL2, IL-4, IL-5, IL-6, IL-10, IL-18, CCL17, TGF-&beta;1, GM-CSF, TNF-&alpha;, and IFN-&gamma;. Overall, our results suggest that, in this hypoxia model, reactive astrogliosis does not alter the inflammatory responses or cause vascular damage in the retina.
dc.description.departmentMolecular Microbiology and Immunology
dc.description.departmentIntegrative Biology
dc.description.departmentSouth Texas Center for Emerging Infectious Diseases
dc.identifierdoi: 10.3390/biom14050567
dc.identifier.citationBiomolecules 14 (5): 567 (2024)
dc.identifier.urihttps://hdl.handle.net/20.500.12588/6481
dc.publisherMDPI
dc.rightsAttribution 4.0 United States
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectdiabetic retinopathy
dc.subjectmicroglia
dc.subjectastrocytes
dc.subjectMüller glia
dc.subjecthypoxia
dc.subjectinflammation
dc.subjectfibrinogen
dc.titleAstrogliosis in the GFAP-CreERT2:Rosa26iDTR Mouse Model Does Not Exacerbate Retinal Microglia Activation or Müller Cell Gliosis under Hypoxic Conditions
dc.typeMDPI

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