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Marina Palmhof, Viktoria Frank, Emely Kortenhorn, Julia Demuth, Gesa Stute, H Burkhard Dick, Stephanie C Joachim; Timeline of retinal degeneration in a model of retinal ischemia. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3202.
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It is known that ischemia-reperfusion (IR) leads to functional and morphological damage of the retina. However, the timeline of degeneration is not well understood yet. Therefore, we investigated the ischemic impact to get a temporal course of the retinal damage.
IR was induced in one eye of rats (140 mmHg for 1h; n=8-10/group). The other eye served as control (Co). 3 and 7d after ischemia ERG measurements were performed. Retinal layers were measured on H&E stained cross-sections 2h, 6h, 12h, 24h, 3d and 7d after IR. Retinal ganglion cells (RGCs) were analyzed using immunohistochemistry (Brn-3a) and qRT-PCR (Pou4f1) at these points in time. Also, the inflammatory response was examined with the cytokines IL1ß, IL6 and TNFα via qRT-PCR. Statistics were performed using student’s t-test.
A significant reduction of ERG a- (p<0.05) and b-wave (p<0.001) amplitudes was noted 3 and 7d after IR. At 6h after IR, a significant decline of the ganglion cell layer thickness was seen (p=0.02), which was remained until day 7 (12h, 24h, 3d, 7d: p<0.001). Significant decrease of the whole retina layer thickness was detected in ischemic eyes starting at 3 days (3d, 7d: p<0.001). Significantly fewer Brn-3a+ cells were noted 24h after IR induction (IR: 35±2 cells/mm; Co: 59±4 cells/mm; p<0.001). This was also observed at 3d (IR: 13±2 cells/mm; Co: 52±3 cells/mm; p<0.001) and 7d (IR: 14±2 cells/mm; Co: 50±3 cells/mm; p<0.001). Also, a significant downregulation of Pou4f1 mRNA levels could be verified 24h (p=0.007), 3d (p=0.006) and 7d (p=0.001) after IR. The upregulation of the cytokines was noticed shortly after IR (24h: IL1ß, TNFα: p<0.01, IL6: p<0.001). IL1β was still upregulated 3d (p=0.03) and 7d (p=0.001) after IR induction, IL6 was again present at day 7 (p<0.001) and TNFα at day 3 (p=0.02).
Our data shows that IR leads to RGC loss at a very early stage on protein and mRNA level, which is still present at later points in time. This cell type seems to be particularly sensitive to IR. Also, a reduction of retinal layer thickness as well as functional loss is detectable early, already after 3 days. We suppose that retinal IR damage appears at a very early point in time and is increasing with time. Interestingly, we could also see an early upregulation of pro-inflammatory cytokines.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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