PMID- 30811545
OWN - NLM
STAT- MEDLINE
DCOM- 20190726
LR  - 20190726
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Linking)
VI  - 60
IP  - 2
DP  - 2019 Feb 1
TI  - Longitudinal In Vivo Characterization of the Streptozotocin-Induced Diabetic 
      Mouse Model: Focus on Early Inner Retinal Responses.
PG  - 807-822
LID - 10.1167/iovs.18-25372 [doi]
AB  - PURPOSE: The goal of this study was to perform an extensive temporal 
      characterization of the early pathologic processes in the streptozotocin 
      (STZ)-induced diabetic retinopathy (DR) mouse model, beyond the vascular 
      phenotype, and to investigate the potential of clinically relevant compounds in 
      attenuating these processes. METHODS: Visual acuity and contrast sensitivity (CS) 
      were studied in the mouse STZ model until 24 weeks postdiabetes onset. ERG, 
      spectral domain optical coherence tomography (SD-OCT), leukostasis, and 
      immunohistochemistry were applied to investigate neurodegeneration, inflammation, 
      and gliosis during early-, mid- and late-phase diabetes. Aflibercept or 
      triamcinolone acetonide (TAAC) was administered to investigate their efficacy on 
      the aforementioned processes. RESULTS: Visual acuity and CS loss started at 4 and 
      18 weeks postdiabetes onset, respectively, and progressively declined over time. 
      ERG amplitudes were diminished and OP latencies increased after 6 weeks, whereas 
      SD-OCT revealed retinal thinning from 4 weeks postdiabetes. Immunohistochemical 
      analyses linked these findings to retinal ganglion and cholinergic amacrine cell 
      loss at 4 and 8 weeks postdiabetes onset, respectively, which was further 
      decreased after aflibercept administration. The number of adherent leukocytes was 
      augmented after 2 weeks, whereas increased micro- and macroglia reactivity was 
      present from 4 weeks postdiabetes. Aflibercept or TAAC showed improved efficacy 
      on inflammation and gliosis. CONCLUSIONS: STZ-induced diabetic mice developed 
      early pathologic DR hallmarks, from which inflammation seemed the initial 
      trigger, leading to further development of functional and morphologic retinal 
      changes. These findings indicate that the mouse STZ model is suitable to study 
      novel integrative non-vascular therapies to treat early DR.
FAU - Sergeys, Jurgen
AU  - Sergeys J
AD  - Neural Circuit Development and Regeneration Research Group, Department of 
      Biology, Zoological Institute, KU Leuven, Leuven, Belgium.
FAU - Etienne, Isabelle
AU  - Etienne I
AD  - Oxurion NV, Leuven, Belgium.
FAU - Van Hove, Inge
AU  - Van Hove I
AD  - Neural Circuit Development and Regeneration Research Group, Department of 
      Biology, Zoological Institute, KU Leuven, Leuven, Belgium.
AD  - Oxurion NV, Leuven, Belgium.
FAU - Lefevere, Evy
AU  - Lefevere E
AD  - Neural Circuit Development and Regeneration Research Group, Department of 
      Biology, Zoological Institute, KU Leuven, Leuven, Belgium.
FAU - Stalmans, Ingeborg
AU  - Stalmans I
AD  - Laboratory of Experimental Ophthalmology, Department of Neurosciences, O&N II, KU 
      Leuven, Leuven, Belgium.
FAU - Feyen, Jean H M
AU  - Feyen JHM
AD  - Oxurion NV, Leuven, Belgium.
FAU - Moons, Lieve
AU  - Moons L
AD  - Neural Circuit Development and Regeneration Research Group, Department of 
      Biology, Zoological Institute, KU Leuven, Leuven, Belgium.
FAU - Van Bergen, Tine
AU  - Van Bergen T
AD  - Oxurion NV, Leuven, Belgium.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Glucocorticoids)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 15C2VL427D (aflibercept)
RN  - 5W494URQ81 (Streptozocin)
RN  - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor)
RN  - F446C597KA (Triamcinolone Acetonide)
MH  - Angiogenesis Inhibitors/therapeutic use
MH  - Animals
MH  - Contrast Sensitivity/*physiology
MH  - Diabetes Mellitus, Experimental/drug therapy/*pathology
MH  - Diabetic Retinopathy/drug therapy/*pathology
MH  - *Disease Models, Animal
MH  - Electroretinography
MH  - Follow-Up Studies
MH  - Glucocorticoids/therapeutic use
MH  - Immunohistochemistry
MH  - Leukostasis
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Receptors, Vascular Endothelial Growth Factor/therapeutic use
MH  - Recombinant Fusion Proteins/therapeutic use
MH  - Retina/*physiopathology
MH  - Streptozocin
MH  - Tomography, Optical Coherence
MH  - Treatment Outcome
MH  - Triamcinolone Acetonide/therapeutic use
MH  - Visual Acuity/*physiology
EDAT- 2019/02/28 06:00
MHDA- 2019/07/28 06:00
CRDT- 2019/02/28 06:00
PHST- 2019/02/28 06:00 [entrez]
PHST- 2019/02/28 06:00 [pubmed]
PHST- 2019/07/28 06:00 [medline]
AID - 2726819 [pii]
AID - 10.1167/iovs.18-25372 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2019 Feb 1;60(2):807-822. doi: 10.1167/iovs.18-25372.