title: Angiography reveals novel features of the retinal vasculature in healthy and diabetic mice.
abstract: The mouse retina is a commonly used animal model for the study of pathogenesis and treatment of blinding retinal vascular diseases such as diabetic retinopathy. In this study, we aimed to characterize normal and pathological variations in vascular anatomy in the mouse retina using fluorescein angiography visualized with scanning laser ophthalmoscopy and optical coherence tomography (SLO-OCT). We examined eyes from C57BL/6J wild type mice as well as the Ins2(Akita) and Akimba mouse models of diabetic retinopathy using the Heidelberg Retinal Angiography (HRA) and OCT system. Angiography was performed on three focal planes to examine distinct vascular layers. For comparison with angiographic data, ex vivo analyses, including Indian ink angiography, histology and 3D confocal scanning laser microscopy were performed in parallel. All layers of the mouse retinal vasculature could be readily visualized during fluorescein angiography by SLO-OCT. Blood vessel density was increased in the deep vascular plexus (DVP) compared with the superficial vascular plexus (SVP). Arteriolar and venular typologies were established and structural differences were observed between venular types. Unexpectedly, the hyaloid artery was found to persist in 15% of C57BL/6 mice, forming anastomoses with peripheral retinal capillaries. Fluorescein leakage was easily detected in Akimba retinae by angiography, but was not observed in Ins2(Akita) mice. Blood vessel density was increased in the DVP of 6 month old Ins2(Akita) mice, while the SVP displayed reduced branching in precapillary arterioles. In summary, we present the first comprehensive characterization of the mouse retinal vasculature by SLO-OCT fluorescein angiography. Using this clinical imaging technique, we report previously unrecognized variations in C57BL/6J vascular anatomy and novel features of vascular retinopathy in the Ins2(Akita) mouse model of diabetes.
authors.affiliation: Centre for Ophthalmology and Visual Science, The University of Western Australia, Crawley, WA 6009, Australia; Ocular Tissue Engineering Laboratory, Lions Eye Institute, 2 Verdun Street, Nedlands, WA 6009, Australia. Electronic address: smclenachan@lei.org.au.
authors.forename: Samuel
authors.initials: S
authors.lastname: McLenachan
authors.affiliation: Centre for Ophthalmology and Visual Science, The University of Western Australia, Crawley, WA 6009, Australia; Department of Molecular Ophthalmology, Lions Eye Institute, Nedlands, WA 6009, Australia.
authors.forename: Aaron Len
authors.initials: AL
authors.lastname: Magno
authors.affiliation: Center of Animal Biotechnology and Gene Therapy (CBATEG), Department of Animal Health and Anatomy, Universitat Autonoma de Barcelona, E-08193 Bellaterra, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Ramos
authors.affiliation: Center of Animal Biotechnology and Gene Therapy (CBATEG), Department of Animal Health and Anatomy, Universitat Autonoma de Barcelona, E-08193 Bellaterra, Spain.
authors.forename: Joana
authors.initials: J
authors.lastname: Catita
authors.affiliation: Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Clayton, VIC 3800, Australia.
authors.forename: Paul G
authors.initials: PG
authors.lastname: McMenamin
authors.affiliation: Centre for Ophthalmology and Visual Science, The University of Western Australia, Crawley, WA 6009, Australia; Ocular Tissue Engineering Laboratory, Lions Eye Institute, 2 Verdun Street, Nedlands, WA 6009, Australia; Ophthalmology Department, Royal Perth Hospital, Wellington Street, Perth, WA 6000, Australia.
authors.forename: Fred Kuanfu
authors.initials: FK
authors.lastname: Chen
authors.affiliation: Centre for Ophthalmology and Visual Science, The University of Western Australia, Crawley, WA 6009, Australia; Department of Molecular Ophthalmology, Lions Eye Institute, Nedlands, WA 6009, Australia.
authors.forename: Elizabeth Piroska
authors.initials: EP
authors.lastname: Rakoczy
authors.affiliation: Center of Animal Biotechnology and Gene Therapy (CBATEG), Department of Animal Health and Anatomy, Universitat Autonoma de Barcelona, E-08193 Bellaterra, Spain; Department of Animal Health and Anatomy, School of Veterinary Medicine, Universitat Autònoma de Barcelona, E-08193 Bellaterra, Spain; Interdisciplinary Centre of Research in Animal Health, Faculty of Veterinary Medicine, Universidade de Lisboa, P-1300-477 Lisbon, Portugal.
authors.forename: Jesus
authors.initials: J
authors.lastname: Ruberte
mesh_terms: D000375:Aging / Q000473:pathology; D000818:Animals; D001160:Arterioles / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D002199:Capillary Permeability; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D003930:Diabetic Retinopathy / Q000473:pathology*; D005451:Fluorescein Angiography; D021621:Imaging, Three-Dimensional; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009887:Ophthalmoscopy; D015861:Retinal Neovascularization / Q000473:pathology; D012171:Retinal Vessels / Q000033:anatomy & histology / Q000473:pathology*; D041623:Tomography, Optical Coherence; D014699:Venules / Q000473:pathology
chemical_list: D015415:Biomarkers
keywords: Akimba; Angiography; Diabetic retinopathy; Hyaloid artery; Ins2(Akita); Mouse; Optical coherence tomography; Retinal vasculature