Poster Malgorzata Nita

Purpose:

The aim of the study was to evaluate the effect of loading doses of ranibizumab on gene expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in patients with CNV/AMD.

Setting:

Study was conducted by the Department of Ophthalmology, Medical University of Silesia, Independent Public Clinical Hospital, Katowice, Poland.

Methods Inclusion criteria: patients ≥60 years old, BCVA 20/40 to 20/320 (Snellen equivalent), not treated before and active CNV in biomicroscope and in optical coherence tomography (OCT).

Exclusion criteria:

Idiopathic CNV, polypoidal choroidal vasculopathy, retinal angiomatous proliferations, coexisting diabetic maculopathy, epiretinal membrane, retinal vein occlusion. Exams of the best-corrected visual acuity, applanation tonometry, indirect biomicroscopy, OCT as well as fluorescein/indocyanine green angiography (if diagnostic necessary) were performed before and after injections. Intravitreal Lucentis ® injections were given three times, at intervals of 4 weeks. Venous blood samples were collected into EDTA-containing tubes before and after third injection. Total RNA concentration was determined by spectrophotometric measurement in 5 µl capillary tubes using the Gene Quant II RNA/DNA Calculator (Pharmacia Biotech, Cambridge, UK). The analysis of genes’ expression profile of MMPs and TIMPs in samples was performed using commercially available oligonucleotide microarrays of HG-U133A (Affymetrix, Santa Clara, CA) according to the manufacturer’s recommendations. The expression profile of selected genes was analyzed before and after third injection.

Results:

Genes encoding MMP-15 (FC 2.22, p=0.0018) and ADAM8 (FC 3.24, p=0.0001) showed overexpression after loading dose of ranibizumab. Expression of genes encoding MMP-12 (FC 2.65, p<0.0001), ADAM5P (FC 3.79, p<0.0001) and TIMP-3 (FC 2.19, p=0.014) dropped down under influence of anty-VEGF therapy. Conclusions Intravitreal anty-VEGF therapy in patients with CNV/AMD has influence on the extracellular matrix gene expression. Loading dose of Lucentis® changes expression of metalloproteinases and their tissue inhibitors. The authors have no financial or proprietary interest in any of the products or techniques mentioned in this paper.