Biochemistry/Molecular Biology - ARVO

ARVO 2013 Annual Meeting Abstracts by Scientific Section/Group - Biochemistry/Molecular Biologyphenotype of Tg and age-matched wild-type (Wt) mice in 18- to 24-month-old mice. Real time PCR, immunohistology, transmissionelectron microscopy and fluorescein angiography (FA) were used toanalyze the phenotype of this transgenic mouse model and agematchedcontrols.Results: This BMP4 over-expressing mouse accumulated remarkableamounts of oxidized lipid in RPE and on Bruch’s membrane (BM).This suggests that over-expressed BMP4 induces oxidative stress ofRPE which might lead to subsequent AMD phenotypes, includingRPE atrophy and thickened BM. RPE in Tg mice showed decreasedheight, hypo- or hyper-pigmentation, disorganized basal infoldingsand cellular lipid vesicles. Some Tg mice eventually developedchoroidal neovascularization (CNV) with fluorescein leakage on FA,isolectin B4 positive staining on flat mounted posterior eye cups andCNV-like lesions by histology. These changes were not seen in aged-matched controls.Conclusions: The BMP4 over-expressing mice mimic thepathological process of AMD and may be a good model for studyingAMD. Our work suggests that a dysregulated growth factor, BMP4,may be involved in the pathogenesis of AMD.Commercial Relationships: Danhong Zhu, None; Jing Xu, None;Xuemei Deng, None; Jamie Hsiung, None; Stephen J. Ryan,Alergan (S); David R. Hinton, RPT (I), RPT (P)Support: EY03040Program Number: 4590 Poster Board Number: A0109Presentation Time: 11:00 AM - 12:45 PMVitamin D Status and Subretinal Fibrosis in Neovascular Age-Related Macular DegenerationAmardeep Singh 1, 2 , Mads K. Falk 1, 2 , Yousif Subhi 1, 2 , Torben L.Sørensen 1, 2 . 1 Ophthalmology, Copenhagen University HospitalRoskilde, Roskilde, Denmark; 2 University of Copenhagen,Copenhagen, Denmark.Purpose: Vitamin D has been shown to have anti-fibrotic propertiesand deficient levels of circulating 25-hydroxyvitamin D have beenassociated with fibrogenesis in several extra-ocular tissues. Evidencelinking vitamin D deficiency to age-related macular degeneration(AMD) is inconsistent. Thus, we sought to investigate 25-hydroxyvitamin D levels across clinical subgroups of AMD andwhether the presence of subretinal fibrosis in neovascular AMD atdiagnosis is associated with lower levels of circulating vitamin D.Methods: Plasma samples were collected from 202 participantsacross 4 groups: controls (n=73), early AMD (n=22), geographicatrophy (n=12) and neovascular AMD (n=95). All participants weresubjected to a structured interview and retinal examination wasperformed using stereoscopic funduscopy on mydriatic eyes, digitalcolor fundoscopy, autofluorescence imaging, spectral-domain opticalcoherence tomography and fluorescein and indocyanin greenangiography in patients suspected of having neovascular age-relatedmacular degeneration. Clinical grading was performed using theClinical Age-Related Maculopathy Grading System. Venous bloodwas obtained for measurement of 25-hydroxyvitamin D2 and D3 inplasma using liquid chromatography-tandem mass spectrometry.Genomic DNA was extracted from leukocytes and genotyping wasperformed for single nucleotide polymorphisms in the vitamin Dmetabolism.Results: Patients with subretinal fibrosis in addition to neovascularAMD had significantly lower levels of circulating 25-hydroxyvitaminD compared to patients without subretinal fibrosis (47.2 versus 75.6nmol/L, p