Dataset Information

Retinal angiogenesis in the Ins2(Akita) mouse model of diabetic retinopathy.

ABSTRACT: PURPOSE:Diabetic retinopathy (DR) is the leading cause of blindness among working age adults and does not have any curative treatments. Although chemical- and injury-induced models of retinal neovascularization exist, the need for a genetic model that closely simulates the DR pathologic process is great. METHODS:Here we characterize the development of the retinal disease phenotype in a genetic model of type 1 diabetes, the Ins2(Akita) mouse, using structural, biochemical, molecular biological, and functional techniques. RESULTS:This model exhibits hyperglycemia by 2 months of age and by 6 months we detect retinal complications in Ins2(Akita) males, including early signs of vascular damage consistent with DR, specifically the appearance of pericyte ghosts, vascular leakage, and microaneurysm formation. By 9 months of age, these changes are accompanied by later vascular signs of DR, specifically retinal neovascularization, formation of new capillary beds, and the presence of new blood vessels abnormally localized in the outer plexiform layer. Consistent with the debilitating effects of such vasculopathy, we also observe increased retinal apoptosis and decreased retinal function measured by electroretinogram. CONCLUSIONS:These data indicate that the Ins2(Akita) mouse is a good model for later-onset DR, modeling both early and some late disease signs. Furthermore, this work suggests that this model may be suitable for testing and development of targeted DR therapies.

SUBMITTER: Han Z

PROVIDER: S-EPMC3558298 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Retinal angiogenesis in the Ins2(Akita) mouse model of diabetic retinopathy.

Han Zongchao Z Guo Junjing J Conley Shannon M SM Naash Muna I MI

Investigative ophthalmology & visual science 20130117 1

<h4>Purpose</h4>Diabetic retinopathy (DR) is the leading cause of blindness among working age adults and does not have any curative treatments. Although chemical- and injury-induced models of retinal neovascularization exist, the need for a genetic model that closely simulates the DR pathologic process is great.<h4>Methods</h4>Here we characterize the development of the retinal disease phenotype in a genetic model of type 1 diabetes, the Ins2(Akita) mouse, using structural, biochemical, molecula ...[more]

PMID: 23221078

Similar Datasets

Project description:BackgroundEarly-stage diabetic retinopathy (DR) is characterized by neurovascular defects. In this study, we hypothesized that human adipose-derived stem cells (ASCs) positive for the pericyte marker CD140b, or their secreted paracrine factors, therapeutically rescue early-stage DR features in an Ins2Akita mouse model.MethodsIns2Akita mice at 24 weeks of age received intravitreal injections of CD140b-positive ASCs (1000 cells/1 μL) or 20× conditioned media from cytokine-primed ASCs (ASC-CM, 1 μL). Age-matched wildtype mice that received saline served as controls. Visual function experiments and histological analyses were performed 3 weeks post intravitreal injection. Biochemical and molecular analyses assessed the ASC-CM composition and its biological effects.ResultsThree weeks post-injection, Ins2Akita mice that received ASCs had ameliorated decreased b-wave amplitudes and vascular leakage but failed to improve visual acuity, whereas Ins2Akita mice that received ASC-CM demonstrated amelioration of all aforementioned visual deficits. The ASC-CM group demonstrated partial amelioration of retinal GFAP immunoreactivity and DR-related gene expression but the ASC group did not. While Ins2Akita mice that received ASCs exhibited occasional (1 in 8) hemorrhagic retinas, mice that received ASC-CM had no adverse complications. In vitro, ASC-CM protected against TNFα-induced retinal endothelial permeability as measured by transendothelial electrical resistance. Biochemical and molecular analyses demonstrated several anti-inflammatory proteins including TSG-6 being highly expressed in cytokine-primed ASC-CM.ConclusionsASCs or their secreted factors mitigate retinal complications of diabetes in the Ins2Akita model. Further investigation is warranted to determine whether ASCs or their secreted factors are safe and effective therapeutic modalities long-term as current locally delivered therapies fail to effectively mitigate the progression of early-stage DR. Nonetheless, our study sheds new light on the therapeutic mechanisms of adult stem cells, with implications for assessing relative risks/benefits of experimental regenerative therapies for vision loss.

Dataset Information

Retinal angiogenesis in the Ins2(Akita) mouse model of diabetic retinopathy.

Publications

Retinal angiogenesis in the Ins2(Akita) mouse model of diabetic retinopathy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets