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Photoreceptor Degeneration Accompanies Vascular Changes in a Zebrafish Model of Diabetic Retinopathy
Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
Univ Zurich, Switzerland.
Linköping University, Department of Biomedical and Clinical Sciences, Division of Speech Therapy, Otorhinolaryngology and Audiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.ORCID iD: 0000-0003-1079-4361
Univ Innsbruck, Austria.
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2020 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 61, no 2, article id UNSP 43Article in journal (Refereed) Published
Abstract [en]

PURPOSE. Diabetic retinopathy (DR) is a leading cause of vision impairment and blindness worldwide in the working-age population, and the incidence is rising. Until now it has been difficult to define initiating events and disease progression at the molecular level, as available diabetic rodent models do not present the full spectrum of neural and vascular pathologies. Zebrafish harboring a homozygous mutation in the pancreatic transcription factor pdx1 were previously shown to display a diabetic phenotype from larval stages through adulthood. In this study, pdx1 mutants were examined for retinal vascular and neuronal pathology to demonstrate suitability of these fish for modeling DR. METHODS. Vessel morphology was examined in pdx1 mutant and control fish expressing the fli1a:EGFP transgene. We further characterized vascular and retinal phenotypes in mutants and controls using immunohistochemistry, histology, and electron microscopy. Retinal function was assessed using electroretinography. RESULTS. Pdx1 mutants exhibit clear vascular phenotypes at 2 months of age, and disease progression, including arterial vasculopenia, capillary tortuosity, and hypersprouting, could be detected at stages extending over more than 1 year. Neural-retinal pathologies are consistent with photoreceptor dysfunction and loss, but do not progress to blindness. CONCLUSIONS. This study highlights pdx1 mutant zebrafish as a valuable complement to rodent and other mammalian models of DR, in particular for research into the mechanistic interplay of diabetes with vascular and neuroretinal disease. They are furthermore suited for molecular studies to identify new targets for treatment of early as well as late DR.

Place, publisher, year, edition, pages
ASSOC RESEARCH VISION OPHTHALMOLOGY INC , 2020. Vol. 61, no 2, article id UNSP 43
Keywords [en]
zebrafish; diabetic retinopathy; diabetes; pdx1
National Category
Ophthalmology
Identifiers
URN: urn:nbn:se:liu:diva-164682DOI: 10.1167/iovs.61.2.43ISI: 000517748100043PubMedID: 32106290OAI: oai:DiVA.org:liu-164682DiVA, id: diva2:1417550
Note

Funding Agencies|Svenska Sallskapet for Medicinsk Forskning; Linkoping University; Loo och Hans Ostermans Stiftelse; Eva och Oscar Ahrens Stiftelse; Stiftelsen Sigurd och Elsa Goljes Minne; Magnus Bergvalls Stiftelse; Ogonfonden; Jeanssons Stiftelser; VetenskapsradetSwedish Research Council; University of Innsbruck; Austrian Science Fund (FWF)Austrian Science Fund (FWF) [P25659-B19, P 30038-BBL]

Available from: 2020-03-29 Created: 2020-03-29 Last updated: 2020-04-22

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Ali, ZaheerLagali, NeilMukwaya, AnthonnyJensen, Lasse
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Division of Cardiovascular MedicineFaculty of Medicine and Health SciencesDivision of Speech Therapy, Otorhinolaryngology and AudiologyDepartment of Ophthalmology in LinköpingDivision of Diagnostics and Specialist MedicineDepartment of Clinical Pharmacology
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