Purchase this article with an account.
Allen C Clermont, Nivetha Murugesan, Edward P Feener; Vascular endothelial growth factor (VEGF)- and the kallikrein kinin system (KKS)- induced neuronal dysfunction in a rodent model of retinal edema.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5487.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Previously, we have shown that VEGF induced retinal vascular permeability (RVP) and thickening is ameliorated in a rodent model of plasma kallikrein (PKal) deficiency. In addition, PKal can directly induce RVP and thickening suggesting that PKal may contribute to both VEGF -mediated and VEGF-independent effects on diabetic macular edema. However, little is known regarding the effects of the KKS on neuroretinal function. The current study examines and compared the effects of VEGF and KKS on the neuroretinal function in rodents with retinal thickening. <br />
Localization of PKal in the retina was observed in retinal histological slices by immunoblotting for CD31 and PKal (AF2498) at 24 hours after VEGF intravitreal injection (100ng/eye). Retinal neuronal function was measured using full field dark adapted electroretinograms (ERG) at baseline, 24 and 48 hours following intravitreal VEGF (10ng/eye), bradykinin (BK, 2µM) or saline (PBS) control. Retinal thickness was measured by Spectral Domain-OCT (Bioptigen 840). <br />
Immunohistochemical staining of the retina reavealed that VEGF injection increased PKal levels through the neuroretina compared with saline injected eyes. In vivo, PBS injection did not alter ERG implicit times or amplitudes at 24 or 48 hours post intravitreal injection (n=9). VEGF (n=7) did not affect ERG at 24 hours but increased signal amplitudes at 48 hours by 67, 63, 71, 77 and 55%, p<0.01 for A-wave and oscillatory potentials 1-4, respectively, compared to baseline. B-wave amplitude increased by 69% (586±45 vs 347±30 µV, p<0.001). Retinal thickness increased in response to VEGF by 18% (239±5 versus 202±5 µm, p<0.001) compared to PBS injection. A positive correlation was observed between B-wave amplitude and total retinal thickness (R2=0.598, p=0.024). Similarly, BK increased B-wave signal amplitudes by 38.8% (482.73 ± 42.3µV) compared to baseline at 48 hours.
This study shows that VEGF causes increased levels of PKal throughout the neuroretina. The KKS and its neuropeptide BK may mediate, in part, VEGF-dependent and -independent neuroretinal dysfunction in retinal edema.<br />
This PDF is available to Subscribers Only