Veronika Matušková1, Vladimir J Balcar2, Naim A Khan3, Ondřej Bonczek4, Laura Ewerlingová4, Tomáš Zeman4, Petr Kolář1, Daniela Vysloužilová1, Eva Vlková1, Omar Šerý4,5. 1. a Department of Ophthalmology , University Hospital Brno and Medical Faculty, Masaryk University , Brno , Czech Republic. 2. b Bosch Institute and Discipline of Anatomy and Histology, School of Medical Sciences , Sydney Medical School, The University of Sydney , Sydney , New South Wales , Australia. 3. c Physiologie de la Nutrition et Toxicologie , UMR U866 INSERM/Université de Bourgogne/Agro-Sup , Dijon , France. 4. d Laboratory of Neurobiology and Molecular Psychiatry, Department of Biochemistry, Faculty of Science , Masaryk University , Brno , Czech Republic. 5. e Institute of Animal Physiology and Genetics , Academy of Sciences of the Czech Republic , Brno , Czech Republic.
Abstract
BACKGROUND: The wet form of age-related macular degeneration (AMD) is characterized by pathological vascularization of the outer retinal layers. The condition responds to treatment with antibodies against vascular endothelial growth factor (VEGF), but the patients receiving such anti-VEGF therapy sometimes show undesirable acute short-term increases in the intraocular pressure (IOP). The cause of this adverse effect is unknown, and here, we are testing a hypothesis that it is related to CD36 gene polymorphisms. MATERIALS AND METHODS: A group of 134 patients with AMD were given three therapeutic doses of anti-VEGF antibody (ranibizumab) at monthly intervals. Their IOP was measured immediately before and 30 min after each injection. Patients' DNA was analyzed, and the changes in IOP were matched against seven polymorphisms of the CD36 gene. RESULTS: Three polymorphisms were found to be associated with increases in IOP: rs1049673 (p = 0.006), rs3211931 (p = 0.01), and rs1761667 (p = 0.043) at the time of the third injection only. Pronounced elevations (IOP > 25 mmHg) were associated with rs1049673 polymorphism: GC genotype (p < 0.01) and CC genotype (p < 0.05); both increasing the risk 2.6-fold, the presence of C-allele conferring a 1.5-fold greater risk and with rs3211931 polymorphism: AG genotype (p < 0.01) and GG genotype (p < 0.05); increasing the risk 2.6-fold (AG) and 2.7-fold (GG). CONCLUSIONS: CD36 receptor may be involved in mediating the effects of VEGF on IOP. The findings will help to identify the patients at risk of acutely elevated IOP following the anti-VEGF therapy.
BACKGROUND: The wet form of age-related macular degeneration (AMD) is characterized by pathological vascularization of the outer retinal layers. The condition responds to treatment with antibodies against vascular endothelial growth factor (VEGF), but the patients receiving such anti-VEGF therapy sometimes show undesirable acute short-term increases in the intraocular pressure (IOP). The cause of this adverse effect is unknown, and here, we are testing a hypothesis that it is related to CD36 gene polymorphisms. MATERIALS AND METHODS: A group of 134 patients with AMD were given three therapeutic doses of anti-VEGF antibody (ranibizumab) at monthly intervals. Their IOP was measured immediately before and 30 min after each injection. Patients' DNA was analyzed, and the changes in IOP were matched against seven polymorphisms of the CD36 gene. RESULTS: Three polymorphisms were found to be associated with increases in IOP: rs1049673 (p = 0.006), rs3211931 (p = 0.01), and rs1761667 (p = 0.043) at the time of the third injection only. Pronounced elevations (IOP > 25 mmHg) were associated with rs1049673 polymorphism: GC genotype (p < 0.01) and CC genotype (p < 0.05); both increasing the risk 2.6-fold, the presence of C-allele conferring a 1.5-fold greater risk and with rs3211931 polymorphism: AG genotype (p < 0.01) and GG genotype (p < 0.05); increasing the risk 2.6-fold (AG) and 2.7-fold (GG). CONCLUSIONS:CD36 receptor may be involved in mediating the effects of VEGF on IOP. The findings will help to identify the patients at risk of acutely elevated IOP following the anti-VEGF therapy.
Authors: Omar Šerý; Tomáš Zeman; Kateřina Sheardová; Martin Vyhnálek; Hana Marková; Jan Laczó; Jan Lochman; Petr Kralik; Kamila Vrzalová; Radka Dziedzinska; Vladimir J Balcar; Jakub Hort Journal: Sci Rep Date: 2022-06-29 Impact factor: 4.996