Kinuthia, Urbanus Muthai and Moehle, Christoph and Adams, Ralf H. and Langmann, Thomas (2025) Immunomodulation of inflammatory responses preserves retinal integrity in murine models of pericyte-depletion retinopathy. JCI INSIGHT, 10 (15): e184465. ISSN , 2379-3708
Full text not available from this repository. (Request a copy)Abstract
The loss of integrity of the blood retina barrier (BRB) is a key pathological hallmark of vision-threatening complications in diabetic retinopathy (DR). Although DR is considered a microvascular disease, mounting evidence from mouse models and patients show that inflammation is closely connected with microvasculopathy. Inflammatory responses during retinal pathophysiology are often orchestrated by microglia, resident innate immune cells of the retina. However, the precise role of microglia activity during DR pathogenesis remains elusive. Here, we used an anti-PDGFR beta antibody and inducible endothelial cell-specific PDGFB-KO during postnatal development of retinal vasculature to reproduce a key feature of DR pathology in mice. In addition, we applied a minocycline therapy to modulate retinal inflammation. Postnatal depletion of pericytes or loss of PDGFB in retinal vessels altered BRB integrity and triggered secretion of angiogenic and inflammatory factors with concomitant microglia reactivity, which was sustained in retinas of adult mice. Microglia reactivity was accompanied by upregulation of disease-associated genes. Notably, minocycline attenuated the cycle of inflammatory responses in young and mature retinas, thereby preserving retinal vascular and structural integrity in mice. Together, our findings suggest that immunomodulation of microglia-driven inflammatory responses preserves retinal vasculature and maintains BRB integrity in 2 different mouse models of human DR.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DIABETIC MACULAR EDEMA; MICROGLIAL ACTIVATION; MINOCYCLINE; BARRIER; ANGIOGENESIS; VEGF; |
| Subjects: | 500 Science > 570 Life sciences |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Jul 2026 11:53 |
| Last Modified: | 28 Jul 2026 11:53 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67256 |
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