SwePub
Sök i LIBRIS databas

  Extended search

id:"swepub:oai:DiVA.org:oru-65679"
 

Search: id:"swepub:oai:DiVA.org:oru-65679" > Patient-specific in...

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist

Patient-specific induced pluripotent stem cell-derived RPE cells : Understanding the pathogenesis of retinopathy in long-chain 3-hydroxyacyl-CoA dehydrogenase deiciency

Polinati, P. P. (author)
Research Program of Molecular Neurology, Biomedicum 1, University of Helsinki, Helsinki, Finland
Ilmarinen, T. (author)
Institute of Biomedical Technology, University of Tampere, Tampere, Finland; BioMediTech, Tampere, Finland
Trokovic, R. (author)
Research Program of Molecular Neurology, Biomedicum 1, University of Helsinki, Helsinki, Finland
show more...
Hyötyläinen, Tuulia, 1971- (author)
Valtion Teknillinen Tutkimuskeskus (VTT) Technical Research Centre of Finland, Espoo, Finland
Otonkoski, T. (author)
Research Program of Molecular Neurology, Biomedicum 1, University of Helsinki, Helsinki, Finland; Children’s Hospital, Helsinki University Central Hospital, Helsinki, Finland
Suomalainen, A. (author)
Research Program of Molecular Neurology, Biomedicum 1, University of Helsinki, Helsinki, Finland; Children’s Hospital, Helsinki University Central Hospital, Helsinki, Finland
Skottman, H. (author)
Institute of Biomedical Technology, University of Tampere, Tampere, Finland; BioMediTech, Tampere, Finland
Tynitiina, T. (author)
Research Program of Molecular Neurology, Biomedicum 1, University of Helsinki, Helsinki, Finland; Children’s Hospital, Helsinki University Central Hospital, Helsinki, Finland
show less...
 (creator_code:org_t)
Lippincott-Raven Publishers, 2015
2015
English.
In: Investigative Ophthalmology and Visual Science. - : Lippincott-Raven Publishers. - 0146-0404 .- 1552-5783. ; 56:5, s. 3371-3382
  • Journal article (peer-reviewed)
Abstract Subject headings
Close  
  • Purpose: Retinopathy is an important manifestation of trifunctional protein (TFP) deficiencies but not of other defects of fatty acid oxidation. The common homozygous mutation in the TFP α-subunit gene HADHA (hydroxyacyl-CoA dehydrogenase), c.1528G>C, affects the long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) activity of TFP and blindness in infancy. The pathogenesis of the retinopathy is unknown. This study aimed to utilize human induced pluripotent stem cell (hiPSC) technology to create a disease model for the disorder, and to derive clues for retinopathy pathogenesis.Methods: We implemented hiPSC technology to generate LCHAD deficiency (LCHADD) patient-specific retinal pigment epithelial (RPE) monolayers. These patient and control RPEs were extensively characterized for function and structure, as well as for lipid composition by mass spectrometry.Results: The hiPSC-derived RPE monolayers of patients and controls were functional, as they both were able to phagocytose the photoreceptor outer segments in vitro. Interestingly, the patient RPEs had intense cytoplasmic neutral lipid accumulation, and lipidomic analysis revealed an increased triglyceride accumulation. Further, patient RPEs were small and irregular in shape, and their tight junctions were disorganized. Their ultrastructure showed decreased pigmentation, few melanosomes, and more melanolysosomes.Conclusions: We demonstrate that the RPE cell model reveals novel early pathogenic changes in LCHADD retinopathy, with robust lipid accumulation, inefficient pigmentation that is evident soon after differentiation, and a defect in forming tight junctions inducing apoptosis. We propose that LCHADD-RPEs are an important model for mitochondrial TFP retinopathy, and that their early pathogenic changes contribute to infantile blindness of LCHADD.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Oftalmologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Ophthalmology (hsv//eng)

Keyword

Retinopathy
mitochondria
beta oxidation
retinal pigment epithelium

Publication and Content Type

ref (subject category)
art (subject category)

Find in a library

To the university's database

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist

Search outside SwePub

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Close

Copy and save the link in order to return to this view