June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Simulating diabetic retinopathy in organotypic retinal explant cultures: Comparison of diabetic conditions on early vs. late post-natal retina
Author Affiliations & Notes
  • Francois Paquet-Durand
    Institute for Ophthalmic Research, University of Tuebingen, Tuebingen, Germany
  • Stavros Vagionitis
    Institute for Ophthalmic Research, University of Tuebingen, Tuebingen, Germany
  • Ksenija Martinovic
    Institute for Ophthalmic Research, University of Tuebingen, Tuebingen, Germany
  • Joaquin Valdes
    Universidad de Valparaiso, Valparaiso, Chile
  • Dragana Trifunovic
    Institute for Ophthalmic Research, University of Tuebingen, Tuebingen, Germany
  • Maria Miranda
    Universidad CEU Cardenal Herrera, Valencia, Spain
  • Oliver Schmachtenberg
    Universidad de Valparaiso, Valparaiso, Chile
  • Footnotes
    Commercial Relationships   Francois Paquet-Durand, None; Stavros Vagionitis, None; Ksenija Martinovic, None; Joaquin Valdes, None; Dragana Trifunovic, None; Maria Miranda, None; Oliver Schmachtenberg, None
  • Footnotes
    Support  FONDECYT (1120513), the Millennium Institute CINV (ICM P99-037-F), the Kerstan Foundation, the Deutsche Forschungsgemeinschaft (DFG PA1751/7- 1), the Alcon Research Institute, the European Commission [DRUGSFORD: HEALTH-F2-2012-304963], Fundación Gangoiti Barrera.
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 5192. doi:
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      Francois Paquet-Durand, Stavros Vagionitis, Ksenija Martinovic, Joaquin Valdes, Dragana Trifunovic, Maria Miranda, Oliver Schmachtenberg; Simulating diabetic retinopathy in organotypic retinal explant cultures: Comparison of diabetic conditions on early vs. late post-natal retina. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5192.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Diabetic retinopathy (DR) is one of the leading causes of vision impairment worldwide. Unfortunately, DR research is hindered by a lack of disease models that faithfully reproduce the retinal phenotype of diabetes, in particular for type 2 diabetes. Previously, we have shown that a number of aspects of DR can be faithfully reproduced in early (P5) post-natal organotypic retinal explant cultures (Valdés et al., ALTEX 33:459-464, 2016). However, since the retina is not fully developed at this stage, it remains unclear whether the deleterious effects of diabetes-like conditions on the early postnatal retina are representative of mature retinal pathophysiology.

Methods : Mouse retinas were explanted at P14 (around eye opening) and treated from P16 to different with different experimental conditions (i.e. no-insulin, high-glucose, no-insulin + high-glucose, 2-deoxyglucose; 2-DG) to simulate type 1 and 2 diabetic conditions. The treatment effects were assessed on histological preparations using photoreceptor row counts, TUNEL assay for cell death detection, and immunostaining for cone arrestin.

Results : In the no-insulin, high-glucose, and no-insulin + high-glucose treatment paradigms the photoreceptor row counts, numbers of TUNEL, and cone arrestin-positive cells did not change significantly when compared to control. However, the 2-DG treatment significantly increased the numbers of dying TUNEL-positive cells in the outer nuclear layer (ONL; control: 1.22% ± 0.3 STD; 2-DG: 13.76% ± 0.8, p<0.001) and reduced the number of arrestin-positive cones per 100 µM of retinal circumference (control: 4.7 ± 0.7; 2-DG: 0.4 ± 0.3, p<0.001). Yet, the overall photoreceptor row count was not significantly altered (control: 8.0 ± 0.6; 2-DG: 8.1 ± 0.4).

Conclusions : Compared to the early post-natal retina, older retinas responded less strongly to simulated diabetic conditions, yet, cone photoreceptors were highly vulnerable to type I diabetes-like conditions caused by 2-DG treatment. Taken together, we have further validated and extended an in vitro model of DR which may prove useful for studies into the etiopathology of DR and for DR-related drug screening.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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