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Chunhua Jiao, Michael David Abramoff, Kyungmoo Lee, Ipek Oguz, Peter Adamson, Adam Hedberg-Buenz, Michael G Anderson, Elliott Sohn; Diabetes induced neurodegeneration in the retina and the brain of mice are associated and independent of microvasculopathy. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5195.
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Diabetes causes structural changes in the brain, primarily in the cortex, thalamus and caudate and putamen, and these have been ascribed to microvascular changes and ischemia. As we have recently discovered that in the retina, neuroretinal degeneration precedes any form of microvascular damage, we sought to determine whether this retinal neurodegeneration, associated with DM is associated with neural loss in the brain. Performing this study on Lp-PLA2 knockout and control mice allowed us to determine an effect of Lp-PLA2 inhibition on DM-induced neurodegeneration in the retina and brain, as well as an effect on microvasculopathy in the retina.
Male Lp-PLA2-/- (n=30) and Lp-PLA2+/+ (n=30) mice at 12 weeks of age received streptozotocin to induce hyperglycemia. At baseline, 12 and 24 weeks after DM was confirmed, mice underwent OCT imaging, MRI and immunohistologic analysis. Whole mount retinas were used for quantification of pericyte density, acellular capillaries, and ganglion density. NFL/GCL thickness were automatically segmented using our Iowa Reference Algorithms. T-2 MRI scans (Varian 4.7T) were automatically segmented using our fully automated and validated brain segmentation algorithm to quantify total brain, hippocampus and caudate and putamen volume. Statistical analysis was performed in R and GraphPad prism 7.
DM LpPLA2-/- (n=11) had significantly greater pericyte density (*p=0.012), and decrease in acellular capillaries (*p=0.035) compared to DM LpPLA2+/+ control (n=9) at 24 weeks but not at 12 weeks after induction of DM. There was no difference in the number of total cells or ganglion cells at week 12 and 24 post-induction of DM. NFL/GCL complex and brian volume were not significantly different between Lp-PLA2-/- and Lp-PLA2+/+ mice at baseline, weeks 12 and 24. Correlation coefficient (r) was significant between retinal NFL/GCL thickness and total brain volume at 0.32 (95% CI, 0.06 – 0.54), also for specific brain structures: hippocampus with r = 0.37 (95% CI, 0.11 – 0.58) and caudate and putamen with r=0.36 (95% CI, 0.10 – 0.57).
LpPLA2 -/- may be protected against DM-induced retinal vascular loss. No protective effect on retinal neurodegeneration or cerebral neurodegeneration was found in DM Lp-PLA2-/- mice. There may be an association between diabetes induced retinal neurodegeneration and cerebral neurodegeneration.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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