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@ARTICLE{Rsch:835954,
      author       = {Rösch, Sarah and Müller, Frank and Walter, Peter and
                      Werner, Claudia},
      title        = {{P}hotoreceptor degeneration by intravitreal injection of
                      {N}-methyl-{N}-nitrosourea ({MNU}) in rabbits: a pilot
                      study.},
      journal      = {Graefe's archive for clinical and experimental
                      ophthalmology},
      volume       = {255},
      number       = {2},
      issn         = {1435-702X},
      address      = {Berlin},
      publisher    = {Springer},
      reportid     = {FZJ-2017-05086},
      pages        = {317 - 331},
      year         = {2017},
      abstract     = {Pilot study on the attempt to induce selective
                      photoreceptor degeneration in the rabbit eye by intravitreal
                      injection of MNU, facing the difficulties of the evaluation
                      of retinal degeneration by different in-vivo and in-vitro
                      methods in such a large eye animal model.Eight pigmented
                      Chinchilla Bastard rabbits were injected intravitreally with
                      MNU (1 × 1mg/kg body weight (BW), 1 × 2mg/kg BW, 3 ×
                      3mg/kg BW, 1 × 4mg/kg BW, 1 × 6mg/kg BW, and 1 ×
                      DMSO + PBS as control). One, 2, and 3 weeks after
                      injection, the effects on the rabbit retina were examined in
                      vivo using clinical observation (macroscopic images,
                      funduscopy, weighing of the animals), measurement of
                      intraocular pressure (IOP), full-field Electroretinography
                      (ffERG), and spectral-domain Optical Coherence Tomography
                      (sd-OCT). After 3 weeks follow-up, blood samples were
                      taken to evaluate the general health status of the animals,
                      and immunohistochemistry (IH) was performed on sections
                      obtained from six different regions throughout the whole
                      retina to evaluate MNU effects in more detail.It was
                      difficult to observe the effects of MNU on retinal structure
                      by OCT in vivo. Only the temporal quadrant of the retina
                      could be visualized. Therefore, it was indispensible to
                      evaluate the effects of MNU on the retina in vitro by
                      examining six areas of the retina using
                      immunohistochemistry. Furthermore, immunohistochemistry
                      plays a decisive role to evaluate the effects on retinal
                      cells other than photoreceptors while in $H\&E$ staining,
                      namely the cell count of the ONL can be observed. The
                      results obtained in vivo and in vitro in this study mainly
                      follow the results of a previous study in mice. The low
                      doses of MNU (1, 2 mg/kg BW) had no effects on retinal
                      function and morphology, while high doses (4, 6 mg/kg BW)
                      led to retinal changes in combination with significant
                      side-effects (e.g., cataractous changes). Injection of 3
                      mg/kg BW MNU induced selective photoreceptor degeneration.
                      However, the degree of degeneration varied between different
                      parts of the same retina and between retinae of different
                      animals. In two of three animals, a complete loss of ERG
                      potentials was observed. Negative effects on the
                      contralateral eye or on general welfare of the animal were
                      never observed.In rabbits, the intravitreal injection of 3
                      mg/kg BW MNU leads to selective but inhomogeneous
                      photoreceptor degeneration.},
      cin          = {ICS-4},
      ddc          = {610},
      cid          = {I:(DE-Juel1)ICS-4-20110106},
      pnm          = {552 - Engineering Cell Function (POF3-552)},
      pid          = {G:(DE-HGF)POF3-552},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:27866331},
      UT           = {WOS:000394157400012},
      doi          = {10.1007/s00417-016-3531-7},
      url          = {https://juser.fz-juelich.de/record/835954},
}