Title

PROSPECTION OF NEW ANTI-ANGIOGENIC DRUGS BASED ON CHEMICALLY MODIFIED HEPARINS

Introduction

The purpose of this study is to investigate the anti-angiogenic effect of chemically modified heparins (mHep) in vitro and in vivo.

Methods

N-desulfated Re-N-acetylated (N-DRN) was the mHEP used in this study. In vitro assays with endothelial cells were performed after 24 hours of treatment with mHep at 10ng/ml, 100ng/ml and 1000ng/ml or saline. The following tests were performed: cell tube formation, viability, proliferation, migration and adhesion. Choroidal neovascularization (CNV) was induced in rats with laser, followed by intravitreal injection of N-DRN using a microseringe (100 ng/ml, 1000 ng/ml and balanced salt solution). Immunofluorescence analysis was performed with a confocal microscope. The CNV area and perimeter were measured with ImageJ.

Results

Compared to saline, N-DRN demonstrated a statistically significant reduce in cell proliferation, tube formation, migration and adhesion with no changes in cell viability. Mean measures of CNV area were 58.77 x 106 pixels/mm (±13,33 x 106) and 66,64 x 106 pixels/mm (±17,52 x 106) in group 100 and 1000ng/ml, respectively; while in the control group mean area was 70,53 x 106 (± 17,01 x 106). The p-value in the ANOVA analysis was 0.0065. Perimeter analysis also demonstrated statistical difference (p = 0.0235) with the mean measure of 93,55 x 104, 94,23 x 104 and 102 x 104 in the 100ng/mL, 1000ng/mL and control group, respectively.

Discussion

N-desulfated Re-N-acetylated is a potencial drug to treat ocular angiogenesis.

Keywords

Macular Degeneration, Angiogenesis Inhibitors, Drug Therapy, Choroidal Neovascularization, Vascular Endothelial Growth Factor A.

Area

CLINICAL CASE

Authors

VINICIUS FERREIRA KNIGGENDORF, JULIANA LUPORINI DREYFUSS, THATIANE A. RUSSO, MARIA EDUARDA PERRUD SOUSA, ALEX TREIGER GRUPENMACHER, CAIO VINICIUS SAITO REGATIERI