Anti-Vascular Endothelial Growth Factors Protect Retinal Pigment Epithelium Cells Against Oxidation by Modulating Nitric Oxide Release and Autophagy

Background/Aims: the anti-vascular endothelial growth factors (VEGF), Aflibercept and Ranibizumab, are used for the treatment of macular degeneration. Here we examined the involvement of nitric oxide (NO), mitochondria function and of apoptosis/autophagy in their antioxidant effects in human retinal pigment epithelium cells (RPE). Methods: RPE were exposed to Ranibizumab/Aflibercept in the absence or presence of NO synthase (NOS) inhibitor and of autophagy activator/blocker, rapamicyn/3-methyladenine. Specific kits were used for cell viability, NO and reactive oxygen species detection and mitochondrial membrane potential measurement, whereas Western Blot was performed for apoptosis/ autophagy markers and other kinases detection. Results: In RPE cultured in physiological conditions, Aflibercept/Ranibizumab increased NO release in a dose and time-dependent way. Opposite results were obtained in RPE pretreated with hydrogen peroxide. Moreover, both the anti-VEGF agents were able to prevent the fall of cell viability and of mitochondrial membrane potential. Those effects were reduced by the NOS inhibitor and 3-methyladenine and were potentiated by rapamycin. Finally, Aflibercept and Ranibizumab counteracted the changes of apoptosis/autophagy markers, NOS, Phosphatidylinositol-3-Kinase/Protein Kinase B and Extracellular signal–regulated kinases 1/2 caused by peroxidation. Conclusion: Aflibercept and Ranibizumab protect RPE against peroxidation through the modulation of NO release, apoptosis and autophagy

Swept-source optical coherence tomography and optical coherence tomography angiography in acquired toxoplasmic chorioretinitis: a case report

Abstract Purpose To describe swept-source optical coherence tomography and optical coherence tomography angiography retinal changes in a case of acute toxoplasmic chorioretinitis both at the time of diagnosis and after healing. Case presentation A 57-year-old white woman suffering from acquired toxoplasmic chorioretinitis underwent swept-source optical coherence tomography and optical coherence tomography angiography both at the time of diagnosis and after healing. In the acute phase of the disease, swept-source optical coherence tomography clearly showed retinal and choroidal involvement in the superficial retina and in the choroidal swelling. Optical coherence tomography angiography showed a complete loss of deep and superficial capillary networks and of choroidal vessels in the area of the inflammation. After healing, swept-source optical coherence tomography showed a retinal thinning of the area involved, with a subversion of retinal layers and no visible change at the choroid level. On the other hand, optical coherence tomography angiography showed the persistence of a vascular occlusion at the retina and choroid level. Conclusion This is the first case in the optical coherence tomography angiography literature that shows the imaging of toxoplasmic chorioretinal lesions. This case confirms the involvement of the retina and choroid in toxoplasmic uveitis and the disruptive potential of such inflammation. The optical coherence tomography angiography performed after healing showed a persistent ablation of the retina, choriocapillaris, and choroidal vessels. The non-invasive optical coherence tomography angiography imaging technique may have diagnostic and prognostic value in regard to toxoplasmic uveitis

Anti-Vascular Endothelial Growth Factors Protect Retinal Pigment Epithelium Cells Against Oxidation by Modulating Nitric Oxide Release and Autophagy

Background/Aims: the anti-vascular endothelial growth factors (VEGF), Aflibercept and Ranibizumab, are used for the treatment of macular degeneration. Here we examined the involvement of nitric oxide (NO), mitochondria function and of apoptosis/autophagy in their antioxidant effects in human retinal pigment epithelium cells (RPE). Methods: RPE were exposed to Ranibizumab/Aflibercept in the absence or presence of NO synthase (NOS) inhibitor and of autophagy activator/blocker, rapamicyn/3-methyladenine. Specific kits were used for cell viability, NO and reactive oxygen species detection and mitochondrial membrane potential measurement, whereas Western Blot was performed for apoptosis/ autophagy markers and other kinases detection. Results: In RPE cultured in physiological conditions, Aflibercept/Ranibizumab increased NO release in a dose and time-dependent way. Opposite results were obtained in RPE pretreated with hydrogen peroxide. Moreover, both the anti-VEGF agents were able to prevent the fall of cell viability and of mitochondrial membrane potential. Those effects were reduced by the NOS inhibitor and 3-methyladenine and were potentiated by rapamycin. Finally, Aflibercept and Ranibizumab counteracted the changes of apoptosis/autophagy markers, NOS, Phosphatidylinositol-3-Kinase/Protein Kinase B and Extracellular signal–regulated kinases 1/2 caused by peroxidation. Conclusion: Aflibercept and Ranibizumab protect RPE against peroxidation through the modulation of NO release, apoptosis and autophagy