The aim was to investigate the effect of streptozotocin-induced diabetes and rosuvastatin on retinal leukocyte-endothelial cell interactions in rodents. Leukocytes, isolated from the spleens of donor animals and fluorescently-labelled with calcein-AM, were transferred between control, diabetic, rosuvastatin treated control and diabetic, and co-treated rosuvastatin and mevalonate diabetic, mice. Fluorescent leukocytes were imaged in the retinas of syngeneic recipients using a scanning laser ophthalmoscope (SLO) and recorded. After imaging animals were infused with 2% Evans Blue, killed and eyes removed and fixed in 2% paraformaldehyde. Retinas were flat mounted and examined for fluorescent cells under a confocal microscope. 2 weeks of STZ-diabetes caused an increase in retinal leukocyte adhesion <i>in vivo</i> and in <i>ex vivo</i> whole mounts, due to alterations to the leukocytes and to the endothelium. Treatment of donor and recipient diabetic animals with rosuvastatin prevented and reversed this increase, as did prevention treatment of recipient diabetic animals only. However, treatment of donor diabetic animals only had no effect. Co-treatment with mevalonate abrogated the effect of rosuvastatin. Rosuvastatin treatment had no effect on plasma cholesterol or triglyceride levels. These results confirm previous reports indicating that leukocyte adhesion is, in part at least, responsible for the capillary occlusions that occur in DR. Rosuvastatin may be effective in the treatment of DR by preventing leukocyte adhesion to the vascular endothelium in retinal vessels. Rosuvastatin appears to exert its effects on the endothelium and its effects are independent of lipid-lowering but dependent upon cholesterol biosynthesis inhibition.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:439898 |
| Date | January 2006 |
| Creators | Waddell, Jennifer Margaret |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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