June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Vascular endothelial growth factor (VEGF) induces retinal edema and neuroretinal dysfunction in diabetic rats.
Author Affiliations & Notes
  • Allen C Clermont
    Beetham Eye Institute, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Nivetha Murugesan
    Kalvista Pharmaceuticals, Inc, Cambridge, Massachusetts, United States
  • Lloyd P Aiello
    Beetham Eye Institute, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Allen Clermont, None; Nivetha Murugesan, Kalvista Pharmaceuticals, Inc (E); Lloyd Aiello, None
  • Footnotes
    Support  Massachusetts Lions Eye Research Fund
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 1385. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      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.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : 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.

Methods : 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).

Results : 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.

Conclusions : 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.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×