Title

EFFICACY OF NEW ANTI-ANGIOGENIC DRUGS DERIVED FROM HEPARINOMIMETICS FOR CHOROIDAL NEOVASCULARIZATION IN AN ANIMAL MODEL

Introduction

Choroidal neovascularization is a common endpoint in key retinal pathologies, such as Diabetic Retinopathy and Age-related Macular Degeneration, with great clinical and social burden worldwide. Many drugs are currently being studied as potential targets, and chemically modified heparins (mHEP) have shown promising anti-angiogenic proprieties. This study aims to test the efficacy of a mHEP as an anti-angiogenic factor in an animal model.

Methods

16 Zucker male pigmented rats were divided into 4 different groups: control group, 0,05mg/mL mHEP, 0,5mg/mL mHEP and 5,0 mg/mL mHEP. Choroidal neovascularization was induced in the animal with the use of argon green laser causing Bruch`s membrane thermal rupture. Animals were then injected with different concentrations of mHEP. On day 15, animals were euthanized and the eyes removed and fixed in formaldehyde. An "eye-cup" model of the choroid was created and anti-VEGF immunofluorescence applied to the specimens. Visualization in fluorescence microscopy of the choroidal neovascularization networks was performed and measures of area and perimeter were taken on ImageJ (NIH). Statistical analysis was made on Prism software using ANOVA multivariable analysis and Bonferroni’s Multiple Comparison Test for multivariate analysis. Statistical significance was set on 95% (p<0,05).

Results

Both in the area and perimeter measures, analyses showed a statistical difference between the control group and the mHEP 5,0mg/mL group, but not between control group x 0,05 and group x 0,5 mg/mL and neither in comparison inside the different drug concentration groups.

Discussion

Modified heparins are molecules that combine the advantage of maintaining the heparin-VEGF binding domain, whereas depriving the molecule of its anticoagulant effect, thus providing safe and efficient activity. This study adds to the previously published data on mHEP as a potential drug with an anti-angiogenic consistent effect in choroidal neovascularization.

Keywords

Choroidal neovascularization; Chemically modified heparins; Heparin; Anti-angiogenic;

Area

CLINICAL CASE

Authors

Alex Treiger Grupenmacher, Bianca Oliveira Augusto, Vinicius Kniggendorf, Diego Lisboa Araújo, Felipe Picanço Muralha, Juliana Luporini Dreyfuss, Caio Vinicius Saito Regatieri