title: Non-invasive assessment of retinal alterations in mouse models of infantile and juvenile neuronal ceroid lipofuscinosis by spectral domain optical coherence tomography.
abstract: BACKGROUND
  The neuronal ceroid lipofuscinoses constitute a group of fatal inherited lysosomal storage diseases that manifest in profound neurodegeneration in the CNS. Visual impairment usually is an early symptom and selective degeneration of retinal neurons has been described in patients suffering from distinct disease subtypes. We have previously demonstrated that palmitoyl protein thioesterase 1 deficient (Ppt1-/-) mice, a model of the infantile disease subtype, exhibit progressive axonal degeneration in the optic nerve and loss of retinal ganglion cells, faithfully reflecting disease severity in the CNS. Here we performed spectral domain optical coherence tomography (OCT) in Ppt1-/- and ceroid lipofuscinosis neuronal 3 deficient (Cln3-/-) mice, which are models of infantile and juvenile neuronal ceroid lipofuscinosis, respectively, in order to establish a non-invasive method to assess retinal alterations and monitor disease severity in vivo.
  
  
  RESULTS
  Blue laser autofluorescence imaging revealed increased accumulation of autofluorescent storage material in the inner retinae of 7-month-old Ppt1-/- and of 16-month-old Cln3-/- mice in comparison with age-matched control littermates. Additionally, optical coherence tomography demonstrated reduced thickness of retinae in knockout mice in comparison with age-matched control littermates. High resolution scans and manual measurements allowed for separation of different retinal composite layers and revealed a thinning of layers in the inner retinae of both mouse models at distinct ages. OCT measurements correlated well with subsequent histological analysis of the same retinae.
  
  
  CONCLUSIONS
  These results demonstrate the feasibility of OCT to assess neurodegenerative disease severity in mouse models of neuronal ceroid lipofuscinosis and might have important implications for diagnostic evaluation of disease progression and therapeutic efficacy in patients. Moreover, the non-invasive method allows for longitudinal studies in experimental models, reducing the number of animals used for research.
authors.affiliation: Department of Neurology, Developmental Neurobiology, University of Wuerzburg, Josef-Schneider-Str, 11, D-97080 Wuerzburg, Germany. groh_j@ukw.de.
authors.forename: Janos
authors.initials: J
authors.lastname: Groh
authors.forename: David
authors.initials: D
authors.lastname: Stadler
authors.forename: Mathias
authors.initials: M
authors.lastname: Buttmann
authors.forename: Rudolf
authors.initials: R
authors.lastname: Martini
mesh_terms: D000367:Age Factors; D000818:Animals; D004195:Disease Models, Animal; D008562:Membrane Glycoproteins / Q000172:deficiency; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics / Q000473:pathology*; D009474:Neurons / Q000473:pathology / Q000648:ultrastructure; D009900:Optic Nerve / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D012160:Retina / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D013869:Thiolester Hydrolases / Q000172:deficiency; D041623:Tomography, Optical Coherence
chemical_list: C102229:CLN3 protein, mouse; C453730:Crb1 protein, mouse; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D013869:Thiolester Hydrolases; C095299:palmitoyl-protein thioesterase