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Allen C Clermont, Nivetha Murugesan, Lloyd P Aiello; Vascular endothelial growth factor (VEGF) induces retinal edema and neuroretinal dysfunction in diabetic rats.. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1385.
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© ARVO (1962-2015); The Authors (2016-present)
The link between VEGF and visual dysfunction in diabetic macular edema (DME) has not been fully established. Previously, we have shown that VEGF induces both retinal edema and neuronal dysfuntion in non-diabetic (NDM) rats. Edema onset occurs at 24h post intravitreal injection of VEGF, but electroretinogram (ERG) abnomalities were observed at 48h post injection. The increase in VEGF-induced scotopic amplitudes at 48 hours was associated with a visual deficit, as measured by optokinetics. The current study investigates the effect of intravitreal VEGF upon retinal edema and neuronal dysfunction in diabetic (DM) rats by measuring retinal thickening and scotopic ERG responses at 48h post injection.
Diabetes was induced in Sprague Dawley rats by streptozotocin (45mg/kg). After 4 weeks of diabetes, NDM and DM rats received IVT injections (5µL) of VEGF (10ng/µL) or saline (PBS) control. Retinal thickness was measured using spectral domain optical coherence tomography (OCT). Retinal neuronal function was assessed using full field dark-adapted ERG at 48 hours following IVT injection. Maximal scotopic responses were obtained using a 5ms white light flash (1.4x104 cd/m2).
Blood glucose in DM was elevated compared to NDM (498±17 vs 126±2 mg/dl). After 4 weeks of DM, no difference was observed in total retinal thickness (184±2, n=20 vs 181±1µm, n=8 rats) compared to NDM. Diabetes induced changes in implicit time (OP2: 21.4±0.2 vs 20.1±0.3 and OP3: 28.4±0.3 vs 26.5±0.4 ms, p<0.01) and A-wave (124±5 vs 151±12 µV, p<0.05) and B-wave amplitude (241±13 vs 320±25 µV, p<0.05) as compared to NDM. At 48 hours after VEGF injection, total retinal thickness (RPE to RNFL) increased from baseline in NDM by 11% (19.8±4.2 vs 1.8±1.3µm, p<0.001) and DM by 7.2% (13.2±2 vs 4.0±1.0µm, p<0.01) compared to PBS injected eyes. The injection of VEGF increased ERG A- and B-wave amplitudes in NDM by 32.2 & 50% (143±19 to 189±12 µV and 297±40 to 446±26 µV, p<0.05) and in DM by 35.0 & 35.1% (105±12 to 142±14 µV and 209±21 to 283±24 µV, p<0.05), compared to PBS, respectively. VEGF did not have an effect on the prolonged implicit times in DM.
This study demonstrates that VEGF stimulates retinal thickening and increases scotopic ERG amplitudes in diabetes similar to observations in non-diabetic rats.
This is a 2020 ARVO Annual Meeting abstract.
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