The results clearly show that the bevacizumab molecule can penetrate the retina and is also transported into the retinal pigment epithelium, the choroid and, in particular, into photoreceptor outer segments after intravitreal injection of Avastin. Active transport mechanisms seem to be involved.
This is the first electrophysiological demonstration of a visual function deficit in aged Opa1 mice. VEP measurements and retrograde labeling experiments show that the number of RGCs is reduced whereas the remaining RGCs and axons function normally. Taken together, these findings support an ascending progress of degeneration from the soma toward the axon.
Based on the electroretinographic findings, the authors conclude that bevacizumab does not have any toxic effects on the mouse retina and its function. The bevacizumab molecule penetrates the retina quickly. Therefore, it can act safely and very quickly, also in deeper retinal layers after its injection.
5,6-Dihydroxyindole (DHI) is a melanin pigment precursor with antioxidant properties. In the light of a report about cytotoxicity of DHI, the aim of this study was to assess possible toxic effects of DHI on cells related to the eye, such as human ARPE-19 cells and mouse retinal explants. Moreover, DHI was tested on its effects on retinal function in vivo using electroretinography. We found cytotoxicity of DHI against ARPE-19 cells at 100 µM, but not at 10 µM. 10 µM DHI exhibited a slight, though not significant protective activity against UV-A damage in ARPE-19 cells. We found cytoprotection in cultured mouse retinas by 50 µM DHI or its diacetylated derivative 5,6-diacetoxyindole (DAI), respectively. In ERG measurements in vivo, amplitudes were decreased only slightly by 100 µM DHI compared to saline, whereas a better preservation of amplitudes was visible at 10 µM DHI, in particular with respect to cones. In histological sections, more cones were found at 10 µM DHI than at 100 µM DHI. As a conclusion, DHI shows a slight protective effect at 10 µM both in vitro and in vivo. At 100 µM, it shows a strong cytotoxicity in vitro, which is strongly reduced in vivo.
Bevacizumab penetrates quickly into the macula, the retinal veins and the optic nerve after intravitreal injection in the primate eye, and accumulates preferentially and specifically on the vessel walls and inside the photoreceptors localised in the fovea centralis 1 day after injection. Our finding supports the clinically observed rapid effect in the treatment of retinal vein occlusion and macular oedema.
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