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@ARTICLE{Merz:306684,
      author       = {J. Merz and E. Müller and W. Darwisch and R. Fairless$^*$
                      and Y. Wang and S. Vorwald and S. Darwisch and E. R.
                      Curticean and F. Shao and I. Wacker and R. R. Schröder and
                      C. Pitzer and C. Schultz and J.-B. van Klinken and F. M. Vaz
                      and F. Kratzer and K. Schwarz and J. G. Okun and Y. Feng and
                      C. Hopf and M. Islinger},
      title        = {{L}ocal accumulation of very long-chain {PUFA} in plexiform
                      layers associates with retinal dysfunction in a mouse model
                      of peroxisomal {ACBD}5-deficiency.},
      journal      = {Cellular and molecular life sciences},
      volume       = {83},
      number       = {1},
      issn         = {1420-682X},
      address      = {Cham (ZG)},
      publisher    = {Springer International Publishing AG},
      reportid     = {DKFZ-2025-02676},
      pages        = {26},
      year         = {2025},
      note         = {2025 Dec 1;83(1):26},
      abstract     = {Patients deficient in the peroxisomal membrane protein
                      ACBD5 regularly exhibit a dystrophy of the retina along with
                      decline in visual acuity. Despite the prevalent retinal
                      phenotype, information on the pathogenesis of the
                      retinodystrophy is limited. To gain insight into the
                      cellular, subcellular and molecular alterations occurring in
                      the retina, we analyzed an ACBD5-deficient mouse model by
                      immunofluorescence microscopy, electron microscopy,
                      full-field electroretinography (ffERG) and as well as
                      analytical and spatial mass spectrometry (MS)-based
                      lipidomics techniques. Histological results implied that
                      ACBD5-deficient mice exhibit a moderate degeneration of
                      photoreceptor, bipolar, ganglion and retinal pigment
                      epithelial cells accompanied, however, by a prominent
                      activation of astroglia and microglia. Reduced a- and b-wave
                      amplitudes from ffERG point to a severe functional
                      dysregulation of retinal signal transduction with a focus at
                      the level of the information-processing cell of the inner
                      retina. At the lipidome level, very long-chain
                      polyunsaturated fatty acids (VLC-PUFA) accumulated in
                      phosphatidylcholines from retina homogenates, most likely
                      disrupted by a decline in peroxisome functions. Remarkably,
                      as revealed by MALDI MS imaging, these lipidome changes
                      affected neither the whole retina nor the photoreceptor
                      outer segments (POS), where VLC-PUFAs display the highest
                      concentration in phospholipids of POS membrane discs. In
                      contrast, VLC-PUFAs in ACBD5-deficient mice consistently
                      accumulated in the inner retinal region from the outer (OPL)
                      to inner plexiform layer (IPL). In line with
                      VLC-PUFA-accumulations, photoreceptor ribbon synapses in the
                      OPL showed morphological signs of degeneration on the
                      ultrastructural level. Hence, peroxisomal dysfunction
                      appears to affect cell type-specific lipid homeostasis,
                      thereby disrupting local retinal membrane physiology leading
                      to a severe neuroinflammation of the ACBD5-deficient mouse
                      retina.},
      keywords     = {Metabolic disorders (Other) / Peroxisomes (Other) / RDLKD
                      (ACBD5-deficiency) (Other) / Retinodystrophy (Other) / Very
                      long-chain fatty acids (VLCFA) (Other)},
      cin          = {B320 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)B320-20160331 / I:(DE-He78)HD01-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41324649},
      doi          = {10.1007/s00018-025-05971-8},
      url          = {https://inrepo02.dkfz.de/record/306684},
}