VEGF‐Trap is a potent modulator of vasoregenerative responses and protects dopaminergic amacrine network integrity in degenerative ischemic neovascular retinopathy
| Autor: | Vanessa Englmaier, Matina Economopoulou, David A. Juárez López, Martin Schaarschmidt, Henning Morawietz, Anica Kurzbach, József Jászai, Marie Merdausl, Richard Funk, Marius Ader, Kwan H. Au Yeung, Jesus Eduardo Rojo Arias |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Recombinant Fusion Proteins Biochemistry Amacrine cell Mice 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Ischemia medicine Animals Aflibercept Retina business.industry Dopaminergic Neurons Retinal Degeneration Retinal Vessels Retinopathy of prematurity Retinal Diabetic retinopathy Macular degeneration medicine.disease Vasomotor System Receptors Vascular Endothelial Growth Factor 030104 developmental biology medicine.anatomical_structure Animals Newborn chemistry Microvessels Cancer research Female Nerve Net business 030217 neurology & neurosurgery Retinopathy medicine.drug |
| Zdroj: | Journal of Neurochemistry. 153:390-412 |
| ISSN: | 1471-4159 0022-3042 |
| DOI: | 10.1111/jnc.14875 |
| Popis: | Retinal hypoxia triggers abnormal vessel growth and microvascular hyper-permeability in ischemic retinopathies. Whereas vascular endothelial growth factor A (VEGF-A) inhibitors significantly hinder disease progression, their benefits to retinal neurons remain poorly understood. Similar to humans, oxygen-induced retinopathy (OIR) mice exhibit severe retinal microvascular malformations and profound neuronal dysfunction. OIR mice are thus a phenocopy of human retinopathy of prematurity, and a proxy for investigating advanced stages of proliferative diabetic retinopathy. Hence, the OIR model offers an excellent platform for assessing morpho-functional responses of the ischemic retina to anti-angiogenic therapies. Using this model, we investigated the retinal responses to VEGF-Trap (Aflibercept), an anti-angiogenic agent recognizing ligands of VEGF receptors 1 and 2 that possesses regulatory approval for the treatment of neovascular age-related macular degeneration, macular edema secondary to retinal vein occlusion and diabetic macular edema. Our results indicate that Aflibercept not only reduces the severity of retinal microvascular aberrations but also significantly improves neuroretinal function. Aflibercept administration significantly enhanced light-responsiveness, as revealed by electroretinographic examinations, and led to increased numbers of dopaminergic amacrine cells. Additionally, retinal transcriptional profiling revealed the concerted regulation of both angiogenic and neuronal targets, including transcripts encoding subunits of transmitter receptors relevant to amacrine cell function. Thus, Aflibercept represents a promising therapeutic alternative for the treatment of further progressive ischemic retinal neurovasculopathies beyond the set of disease conditions for which it has regulatory approval. Cover Image for this issue: doi: 10.1111/jnc.14743. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text