Abstract:
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.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Ali Z,Zang J,Lagali N,Schmitner N,Salvenmoser W,Mukwaya A,Neuhauss SCF,Jensen LD,Kimmel RAdoi
10.1167/iovs.61.2.43subject
Has Abstractpub_date
2020-02-07 00:00:00pages
43issue
2eissn
0146-0404issn
1552-5783pii
2762335journal_volume
61pub_type
杂志文章abstract:PURPOSE:To assess the reactive changes of the corneal epithelial thickness (ET) profile induced by small incision lenticule extraction (SMILE) for treatment of myopia. METHODS:This prospective observational study included 46 eyes of 23 patients that were scheduled for myopic SMILE. High-resolution spectral-domain opti...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.15-18879
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:10.1167/iovs.10-6667
更新日期:2011-06-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:10.1167/iovs.12-9466
更新日期:2012-04-30 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1998-03-01 00:00:00
abstract:PURPOSE:The prevalence of myopia shows a decline with age in cross-sectional studies. This pattern may represent an increase in the prevalence of myopia in younger generations, possibly through increased exposure to near work, or an intrinsic age-related decline in myopia prevalence. Data were analyzed from published s...
journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:2000-07-01 00:00:00
abstract:PURPOSE:Corneal crystallins are lost from resident cells of the corneal stroma during wound repair, and this is associated with a loss of cell transparency. The goal of this study was to identify factors inducing loss of the corneal crystallin transketolase (TKT). METHODS:A cell culture model of freshly isolated rabbi...
journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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更新日期:2015-06-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:10.1167/iovs.10-5438
更新日期:2010-09-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:10.1167/iovs.05-0723
更新日期:2005-12-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:1986-10-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:1987-04-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:1994-09-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:2016-08-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:2001-11-01 00:00:00
abstract:PURPOSE:Keratoconus is characterized by thinning and scarring of the central region of the cornea. Previous research showed that, in corneas obtained from patients with keratoconus, lysosomal enzyme activities are elevated, whereas levels of protease inhibitors such as alpha1-proteinase inhibitor are reduced. This stud...
journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1998-06-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:1999-09-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:1999-05-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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doi:
更新日期:1981-06-01 00:00:00
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更新日期:2018-12-03 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:1996-07-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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更新日期:1990-04-01 00:00:00