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Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/14788

Title: Abnormal Retinal Vascular Development in a Mouse Model of Fetal & Neonatal Alloimmune Thrombocytopenia (FNAITP) - Beta3 Integrins and a Potential Role for the Ophthalmologist in Neonatal Screening
Authors: Stella Briggs PhD
Keywords: retinal neovascularization • retinal development• receptors
تاريخ النشر: 2007
Publisher: Invest Ophthalmol Vis Sci
Abstract: FNAITP is an immune disorder in which maternal antibodies cross the placenta and bind to platelet surface antigens such as B3 integrin (allbB3) inherited by the fetus from the father. The ensuing platelet lysis carries a major risk of bleeding and intracranial haemorrhage. FNAITP is estimated to affect 111, 000 liveborn neonates to varying degrees. Purpose: Because B3 integrin is also found on endothelial cells, and the retinal vasculature is known to express avB3 integrins, we asked whether a severe form ofFNAITP might also include direct vascular damage or inhibition of angiogenesis, and whether this could be detected by evaluation of the developing retina in a murine model. Methods: Female B3-/- mice were twice immunized with B3+ platelets and mated with wild type males. Rates of miscarriage and neonatal haemorrhage were evaluated, along with maternal and neonatal titres ofanti-B3 antibodies. In a second series, mothers with a history of FNAITP received intravenous IgG (IVlG) once weekly during subsequent pregnancies to determine whether this treatment could reduce antibody-mediated thrombolysis or vascular damage. Quantification of vessel inhibition was performed by wholemount immunohistochemical analysis ofPND2 retina, stained with Lectin SB4 and collagnen composite analyses) were analyzed using the Tukey t-test (in conjunction with one-way ANOVA). Note that the experiment was performed three times to ensure reproducibility. Animals were treated in accordance with ARVO and IACUC guidelines. Results: A total of70 retinas were analyzed, and 513 radial measurements performed. The mean radial growth of the vehicle control vessel was 1015.1 +/- 32~m. For the PTK787 doses, radial growth was 983.4 +/- 43~m (2.5 mg/kg), 804.0 +/-57~m (I0mglkg), 269.8 +/-51~m (25mglkg), 361.6 +/- 45~m (30mglkg), and 221.8 +/-22~m (40mglkg). This represents a growth reduction relative to vehicle of 3.1 , 20.8, 73.4, 64.4, and 78.1 %, respectively. The drug was well tolerated with equivalent losses in control and experimental groups. Conclusions: Systemic administration ofPTK787 blocked RVD in a dose-dependent manner, reaching an inhibition of 78% at maximum dose of 40 mg/kg.
URI: http://hdl.handle.net/123456789/14788
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