Dataset Information

Fewer Functional Deficits and Reduced Cell Death after Ranibizumab Treatment in a Retinal Ischemia Model.

ABSTRACT: Retinal ischemia is an important factor in several eye disorders. To investigate the impact of VEGF inhibitors, as a therapeutic option, we studied these in a retinal ischemia animal model. Therefore, animals received bevacizumab or ranibizumab intravitreally one day after ischemia induction. Via electroretinography, a significant decrease in a- and b-wave amplitudes was detected fourteen days after ischemia, but they were reduced to a lesser extent in the ranibizumab group. Ischemic and bevacizumab retinae displayed fewer retinal ganglion cells (RGCs), while no significant cell loss was noted in the ranibizumab group. Apoptosis was reduced after therapy. More autophagocytotic cells were observed in ischemic and bevacizumab eyes, but not in ranibizumab eyes. Additionally, more microglia, as well as active ones, were revealed in all ischemic groups, but the increase was less prominent under ranibizumab treatment. Fewer cone bipolar cells were detected in ischemic eyes, in contrast to bevacizumab and ranibizumab-treated ones. Our results demonstrate a reduced apoptosis and autophagocytosis rate after ranibizumab treatment. Furthermore, a certain protection was seen regarding functionality, RGC, and bipolar cell availability, as well as microglia activation by ranibizumab treatment after ischemic damage. Thus, ranibizumab could be an option for treatment of retinal ischemic injury.

SUBMITTER: Palmhof M

PROVIDER: S-EPMC6032266 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Fewer Functional Deficits and Reduced Cell Death after Ranibizumab Treatment in a Retinal Ischemia Model.

Palmhof Marina M Lohmann Stephanie S Schulte Dustin D Stute Gesa G Wagner Natalie N Dick H Burkhard HB Joachim Stephanie C SC

International journal of molecular sciences 20180531 6

Retinal ischemia is an important factor in several eye disorders. To investigate the impact of VEGF inhibitors, as a therapeutic option, we studied these in a retinal ischemia animal model. Therefore, animals received bevacizumab or ranibizumab intravitreally one day after ischemia induction. Via electroretinography, a significant decrease in a- and b-wave amplitudes was detected fourteen days after ischemia, but they were reduced to a lesser extent in the ranibizumab group. Ischemic and bevaciz ...[more]

PMID: 29857531

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Project 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.

Project description:BACKGROUND:To identify baseline patient characteristics associated with early clinically significant visual acuity (VA) improvements within 3?months of treatment initiation in ranibizumab-treated patients with retinal vein occlusion (RVO) in the SHORE study. METHODS:Post hoc analysis of baseline patient characteristics in the randomized, open-label, vision examiner-masked SHORE phase 4 study that compared monthly versus pro re nata dosing of ranibizumab in patients with branch and central RVO. Patients who enrolled in SHORE fulfilled eligibility criteria per protocol (N =?202). SHORE data were retrospectively analyzed to identify baseline patient characteristics associated with early clinically significant improvements in VA, defined as improvement to a Snellen equivalent of 20/40 or better vision (? 69 Early Treatment Diabetic Retinopathy Study [ETDRS] letters) or an increase in best-corrected VA (BCVA) of 15 or more ETDRS letters from baseline within 3?months of treatment initiation. Main outcome measures were BCVA gain of 15 or more ETDRS letters from baseline, Snellen equivalent of 20/40 or better vision, and baseline factors associated with early clinically significant improvement in BCVA. RESULTS:The median time for patients to achieve a BCVA of 20/40 or better was 59?days and the median time for patients to gain 15 or more ETDRS letters was 63?days. Better baseline BCVA (>?50 ETDRS letters/Snellen equivalent ??20/100), greater baseline total macular volume (>?9.99?mm3), and presence of subretinal fluid at baseline were all associated with early improvement to 20/40 or better vision (ETDRS equivalent ??69 letters; P <?.0001, P =?.02, and P =?.03, respectively). CONCLUSIONS:This retrospective analysis found that better BCVA, greater total macular volume, and presence of subretinal fluid at baseline were associated with more rapid vision gains. Clinicians may find these helpful when considering the likelihood of achieving early clinically significant VA improvements with ranibizumab in patients with RVO. TRIAL REGISTRATION:ClinicalTrials.gov NCT01277302 .

Dataset Information

Fewer Functional Deficits and Reduced Cell Death after Ranibizumab Treatment in a Retinal Ischemia Model.

Publications

Fewer Functional Deficits and Reduced Cell Death after Ranibizumab Treatment in a Retinal Ischemia Model.

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