September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Characterization of early retinal degeneration in ZDF rats, a genetic model of type 2 diabetes
Author Affiliations & Notes
  • Ivan Fernandez-Bueno
    Instituto Universitario de Oftalmobiologia Aplicada (IOBA), University of Valladolid, Valladolid, Spain
    Centro en Red de Medicina Regenerativa y Terapia Celular, Castille & Leon Regional Government Action, Valladolid, Spain
  • Robert Jones
    RenaSci Limited, Nottingham, United Kingdom
  • Antonio Lopez-Garcia
    Instituto Universitario de Oftalmobiologia Aplicada (IOBA), University of Valladolid, Valladolid, Spain
  • Sharon Cheetham
    RenaSci Limited, Nottingham, United Kingdom
  • Yolanda Diebold
    Instituto Universitario de Oftalmobiologia Aplicada (IOBA), University of Valladolid, Valladolid, Spain
  • Footnotes
    Commercial Relationships   Ivan Fernandez-Bueno, None; Robert Jones, None; Antonio Lopez-Garcia, None; Sharon Cheetham, None; Yolanda Diebold, None
  • Footnotes
    Support  EU Program FP7-PEOPLE-2013-IAPP (612218/3D-NET) Grant. I Fernandez-Bueno was supported by Centro en Red de Medicina Regenerativa y Terapia Celular, Castille & Leon Regional Government Action, Spain
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 2717. doi:
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      Ivan Fernandez-Bueno, Robert Jones, Antonio Lopez-Garcia, Sharon Cheetham, Yolanda Diebold; Characterization of early retinal degeneration in ZDF rats, a genetic model of type 2 diabetes. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2717.

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      © 2017 Association for Research in Vision and Ophthalmology.

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Abstract

Purpose : To characterize retinal degeneration in Obese Zucker diabetic fatty (ZDF) rats, a genetic model of type 2 diabetes, by histological and immunohistochemical evaluation

Methods : Male Lean (?/+; n=6) and Obese ZDF (fa/fa; n=6) rats (Charles River, UK) were used. Animals were maintained under standard laboratory conditions with free access to food and water. At 24 weeks of age blood glucose levels and body weights were determined and animals euthanized. Eyes were enucleated and fixed in 4% paraformaldehyde in phosphate buffer. Whole eye globes were embedded in paraffin wax and vertical serial sections (4μm) through the optic disc were obtained. Ocular sections were stained for hematoxylin and eosin or immunostained for TUNEL and the phenotype-specific markers recoverin, vimentin, glial fibrillary acidic protein (GFAP), retinal pigment epithelium-specific 65 kDa protein (RPE65) and zonula occludens protein 1 (ZO1)

Results : Body weights were not significantly different between Lean (401±6.4g) and Obese (391±4.7g) animals. Blood glucose levels were significantly higher in Obese rats compared to Lean controls (38.0±1.0 and 10.6±0.6mM respectively). Obese ZDF showed enclosed retinal regions with initial morphological degenerative changes, such as ONL and INL disorganization and TUNEL-positive-nuclei in the photoreceptor inner segments area. Recoverin-immunostained photoreceptors and bipolar cells did not show morphological differences between Lean and Obese ZDF; however, a slight reduction in staining intensity was observed in Obese ZDF. Vimentin and GFAP expression was upregulated throughout the cytoplasm of the Müller cells to the ONL in Obese ZDF. In Lean and Obese animals RPE65 was present in the soma of retinal pigment epithelium (RPE) cells. ZO1 was distributed apically to the RPE nuclei of Lean ZDF, while appeared diffuse in the cytoplasm of Obese rats

Conclusions : Early retinal degenerative changes of photoreceptors, bipolar, glial and RPE cells were observed in Obese ZDF rats. This type 2 diabetes animal model may be useful to understand the pathogenesis of diabetic retinopathy as well as to screen the efficacy of neuroprotective drugs in diabetes

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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