title: The TetO rat as a new translational model for type 2 diabetic retinopathy by inducible insulin receptor knockdown.
abstract: Although the renin-angiotensin system plays an important role in the progression of diabetic retinopathy, its influence therein has not been systematically evaluated. Here we test the suitability of a new translational model of diabetic retinopathy, the TetO rat, for addressing the role of angiotensin-II receptor 1 (AT1) blockade in experimental diabetic retinopathy.
  
  
  
  Diabetes was induced by tetracycline-inducible small hairpin RNA (shRNA) knockdown of the insulin receptor in rats, generating TetO rats. Systemic treatment consisted of an AT1 blocker (ARB) at the onset of diabetes, following which, 4-5 weeks later the retina was analysed in vivo and ex vivo. Retinal function was assessed by Ganzfeld electroretinography (ERG).
  
  
  
  Retinal vessels in TetO rats showed differences in vessel calibre, together with gliosis. The total number and the proportion of activated mononuclear phagocytes was increased. TetO rats presented with loss of retinal ganglion cells (RGC) and ERG indicated photoreceptor malfunction. Both the inner and outer blood-retina barriers were affected. The ARB treated group showed reduced gliosis and an overall amelioration of retinal function, alongside RGC recovery, whilst no statistically significant differences in vascular and inflammatory features were detected.
  
  
  
  The TetO rat represents a promising translational model for the early neurovascular changes associated with type 2 diabetic retinopathy. ARB treatment had an effect on the neuronal component of the retina but not on the vasculature.
authors.affiliation: Department of Ophthalmology, Charité-Universitätsmedizin Berlin Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany. nadine.reichhart@charite.de.
authors.forename: Nadine
authors.initials: N
authors.lastname: Reichhart
authors.affiliation: Department of Ophthalmology, Charité-Universitätsmedizin Berlin Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Sergio
authors.initials: S
authors.lastname: Crespo-Garcia
authors.affiliation: Experimental and Clinical Research Center, a cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and the Charité-Universitätsmedizin Berlin, Berlin, Germany.|Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.|Berlin Institute of Health, Berlin, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Haase
authors.affiliation: Experimental and Clinical Research Center, a cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and the Charité-Universitätsmedizin Berlin, Berlin, Germany.|Berlin Institute of Health, Berlin, Germany.|Department of Obstetrics, Charité-Universitätsmedizin Berlin Campus Virchow Klinikum, Berlin, Germany.|Department of Gynecology, Charité-Universitätsmedizin Berlin Campus Virchow Klinikum, Berlin, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Golic
authors.affiliation: Department of Ophthalmology, Charité-Universitätsmedizin Berlin Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Sergej
authors.initials: S
authors.lastname: Skosyrski
authors.affiliation: Department of Ophthalmology, Charité-Universitätsmedizin Berlin Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany.|Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Rübsam
authors.affiliation: Department of Ophthalmology, Charité-Universitätsmedizin Berlin Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Herrspiegel
authors.affiliation: Department of Ophthalmology, Charité-Universitätsmedizin Berlin Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Kociok
authors.affiliation: Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.|German Center for Cardiovascular Disease, Berlin, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Alenina
authors.affiliation: Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.|Berlin Institute of Health, Berlin, Germany.|German Center for Cardiovascular Disease, Berlin, Germany.|Department of Biology, Universität zu Lübeck, Lübeck, Germany.|Charité-Universitätsmedizin Berlin Campus Berlin-Buch, Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.affiliation: Experimental and Clinical Research Center, a cooperation between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and the Charité-Universitätsmedizin Berlin, Berlin, Germany.|Berlin Institute of Health, Berlin, Germany.|Charité-Universitätsmedizin Berlin Campus Berlin-Buch, Berlin, Germany.|Department of Cardiology and Nephrology, HELIOS Klinikum Berlin-Buch, Berlin, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Dechend
authors.affiliation: Department of Ophthalmology, Charité-Universitätsmedizin Berlin Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Strauss
authors.affiliation: Department of Ophthalmology, Charité-Universitätsmedizin Berlin Campus Virchow Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany. antonia.joussen@charite.de.
authors.forename: Antonia M
authors.initials: AM
authors.lastname: Joussen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D016133:Polymerase Chain Reaction; D051381:Rats; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000378:metabolism; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012165:Retinal Ganglion Cells
chemical_list: C524087:Agtrap protein, rat; D011945:Receptors, Angiotensin; D011972:Receptor, Insulin
keywords: Angiotensin-II receptor 1 blockade; Experimental diabetic retinopathy; Neurodegeneration; Translational model; Type 2 diabetes