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Protective effects on the retina after ranibizumab treatment in an ischemia model

Retinal ischemia is common in eye disorders, like diabetic retinopathy or retinal vascular occlusion. The goal of this study was to evaluate the potential protective effects of an intravitreally injected vascular endothelial growth factor (VEGF) inhibitor (ranibizumab) on retinal cells in an ischemi...

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Autores principales: Joachim, Stephanie C., Renner, Marina, Reinhard, Jacqueline, Theiss, Carsten, May, Caroline, Lohmann, Stephanie, Reinehr, Sabrina, Stute, Gesa, Faissner, Andreas, Marcus, Katrin, Dick, H. Burkhard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5553852/
https://www.ncbi.nlm.nih.gov/pubmed/28800629
http://dx.doi.org/10.1371/journal.pone.0182407
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author Joachim, Stephanie C.
Renner, Marina
Reinhard, Jacqueline
Theiss, Carsten
May, Caroline
Lohmann, Stephanie
Reinehr, Sabrina
Stute, Gesa
Faissner, Andreas
Marcus, Katrin
Dick, H. Burkhard
author_facet Joachim, Stephanie C.
Renner, Marina
Reinhard, Jacqueline
Theiss, Carsten
May, Caroline
Lohmann, Stephanie
Reinehr, Sabrina
Stute, Gesa
Faissner, Andreas
Marcus, Katrin
Dick, H. Burkhard
author_sort Joachim, Stephanie C.
collection PubMed
description Retinal ischemia is common in eye disorders, like diabetic retinopathy or retinal vascular occlusion. The goal of this study was to evaluate the potential protective effects of an intravitreally injected vascular endothelial growth factor (VEGF) inhibitor (ranibizumab) on retinal cells in an ischemia animal model via immunohistochemistry (IF) and quantitative real-time PCR (PCR). A positive binding of ranibizumab to rat VEGF-A was confirmed via dot blot. One eye underwent ischemia and a subgroup received ranibizumab. A significant VEGF increase was detected in aqueous humor of ischemic eyes (p = 0.032), whereas VEGF levels were low in ranibizumab eyes (p = 0.99). Ischemic retinas showed a significantly lower retinal ganglion cell number (RGC; IF Brn-3a: p<0.001, IF RBPMS: p<0.001; PCR: p = 0.002). The ranibizumab group displayed fewer RGCs (IF Brn-3a: 0.3, IF RBPMS: p<0.001; PCR: p = 0.007), but more than the ischemia group (IF Brn-3a: p = 0.04, IF RBPMS: p = 0.03). Photoreceptor area was decreased after ischemia (IF: p = 0.049; PCR: p = 0.511), while the ranibizumab group (IF: p = 0.947; PCR: p = 0.122) was comparable to controls. In the ischemia (p<0.001) and ranibizumab group (p<0.001) a decrease of ChAT(+) amacrine cells was found, which was less prominent in the ranibizumab group. VEGF-receptor 2 (VEGF-R2; IF: p<0.001; PCR: p = 0.021) and macroglia (GFAP; IF: p<0.001; PCR: p<0.001) activation was present in ischemic retinas. The activation was weaker in ranibizumab retinas (VEGF-R2: IF: p = 0.1; PCR: p = 0.03; GFAP: IF: p = 0.1; PCR: p = 0.015). An increase in the number of total (IF: p = 0.003; PCR: p = 0.023) and activated microglia (IF: p<0.001; PCR: p = 0.009) was detected after ischemia. These levels were higher in the ranibizumab group (Iba1: IF: p<0.001; PCR: p = 0.018; CD68: IF: p<0.001; PCR: p = 0.004). Our findings demonstrate that photoreceptors and RGCs are protected by ranibizumab treatment. Only amacrine cells cannot be rescued. They seem to be particularly sensitive to ischemic damage and need maybe an earlier intervention.
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spelling pubmed-55538522017-08-25 Protective effects on the retina after ranibizumab treatment in an ischemia model Joachim, Stephanie C. Renner, Marina Reinhard, Jacqueline Theiss, Carsten May, Caroline Lohmann, Stephanie Reinehr, Sabrina Stute, Gesa Faissner, Andreas Marcus, Katrin Dick, H. Burkhard PLoS One Research Article Retinal ischemia is common in eye disorders, like diabetic retinopathy or retinal vascular occlusion. The goal of this study was to evaluate the potential protective effects of an intravitreally injected vascular endothelial growth factor (VEGF) inhibitor (ranibizumab) on retinal cells in an ischemia animal model via immunohistochemistry (IF) and quantitative real-time PCR (PCR). A positive binding of ranibizumab to rat VEGF-A was confirmed via dot blot. One eye underwent ischemia and a subgroup received ranibizumab. A significant VEGF increase was detected in aqueous humor of ischemic eyes (p = 0.032), whereas VEGF levels were low in ranibizumab eyes (p = 0.99). Ischemic retinas showed a significantly lower retinal ganglion cell number (RGC; IF Brn-3a: p<0.001, IF RBPMS: p<0.001; PCR: p = 0.002). The ranibizumab group displayed fewer RGCs (IF Brn-3a: 0.3, IF RBPMS: p<0.001; PCR: p = 0.007), but more than the ischemia group (IF Brn-3a: p = 0.04, IF RBPMS: p = 0.03). Photoreceptor area was decreased after ischemia (IF: p = 0.049; PCR: p = 0.511), while the ranibizumab group (IF: p = 0.947; PCR: p = 0.122) was comparable to controls. In the ischemia (p<0.001) and ranibizumab group (p<0.001) a decrease of ChAT(+) amacrine cells was found, which was less prominent in the ranibizumab group. VEGF-receptor 2 (VEGF-R2; IF: p<0.001; PCR: p = 0.021) and macroglia (GFAP; IF: p<0.001; PCR: p<0.001) activation was present in ischemic retinas. The activation was weaker in ranibizumab retinas (VEGF-R2: IF: p = 0.1; PCR: p = 0.03; GFAP: IF: p = 0.1; PCR: p = 0.015). An increase in the number of total (IF: p = 0.003; PCR: p = 0.023) and activated microglia (IF: p<0.001; PCR: p = 0.009) was detected after ischemia. These levels were higher in the ranibizumab group (Iba1: IF: p<0.001; PCR: p = 0.018; CD68: IF: p<0.001; PCR: p = 0.004). Our findings demonstrate that photoreceptors and RGCs are protected by ranibizumab treatment. Only amacrine cells cannot be rescued. They seem to be particularly sensitive to ischemic damage and need maybe an earlier intervention. Public Library of Science 2017-08-11 /pmc/articles/PMC5553852/ /pubmed/28800629 http://dx.doi.org/10.1371/journal.pone.0182407 Text en © 2017 Joachim et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Joachim, Stephanie C.
Renner, Marina
Reinhard, Jacqueline
Theiss, Carsten
May, Caroline
Lohmann, Stephanie
Reinehr, Sabrina
Stute, Gesa
Faissner, Andreas
Marcus, Katrin
Dick, H. Burkhard
Protective effects on the retina after ranibizumab treatment in an ischemia model
title Protective effects on the retina after ranibizumab treatment in an ischemia model
title_full Protective effects on the retina after ranibizumab treatment in an ischemia model
title_fullStr Protective effects on the retina after ranibizumab treatment in an ischemia model
title_full_unstemmed Protective effects on the retina after ranibizumab treatment in an ischemia model
title_short Protective effects on the retina after ranibizumab treatment in an ischemia model
title_sort protective effects on the retina after ranibizumab treatment in an ischemia model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5553852/
https://www.ncbi.nlm.nih.gov/pubmed/28800629
http://dx.doi.org/10.1371/journal.pone.0182407
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