title: Early alteration of retinal neurons in Aipl1-/- animals.
abstract: OBJECTIVE
  Mutations in the photoreceptor cell-specific gene encoding aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1) lead to Leber congenital amaurosis (LCA4), retinitis pigmentosa, and cone-rod dystrophy. Gene therapy appears to be promising in the treatment for AIPL1-mediated vision loss in humans. Prior to initiating these treatments, however, it is crucial to understand how the retinal neurons remodel themselves in response to photoreceptor cell degeneration. In this study, using an animal model for AIPL1-LCA, Aipl1(-/-) mice, we investigate the changes in postreceptoral retinal neurons during the course of photoreceptor cell loss.
  
  
  METHODS
  Morphology of the Aipl1(-/-) retina from postnatal day 8 to 150 was compared to that of age-matched, wild-type C57Bl6/J retina (WT) by immunocytochemistry using cell-specific markers.
  
  
  RESULTS
  Expression of postsynaptic proteins in bipolar cells is reduced prior to photoreceptor cell degeneration at postnatal day 8. Bipolar and horizontal cells retract their dendrites. Cell bodies and axons of bipolar and horizontal cells are disorganized during the course of degeneration. Müller cell processes become hypertrophic and form a dense fibrotic layer outside the inner nuclear layer.
  
  
  CONCLUSIONS
  An early defect in photoreceptor cells in the AIPL1-LCA mouse model affects the expression of postsynaptic markers, suggesting abnormal development of bipolar synapses. Once degeneration of photoreceptor cells is initiated, remodeling of retinal neurons in the Aipl1(-/-) animal is rapid.
authors.affiliation: Departments of Ophthalmology and Biochemistry, Center for Neuroscience, West Virginia University, Morgantown, West Virginia, United States.
authors.forename: Ratnesh Kumar
authors.initials: RK
authors.lastname: Singh
authors.affiliation: Departments of Ophthalmology and Biochemistry, Center for Neuroscience, West Virginia University, Morgantown, West Virginia, United States.
authors.forename: Saravanan
authors.initials: S
authors.lastname: Kolandaivelu
authors.affiliation: Departments of Ophthalmology and Biochemistry, Center for Neuroscience, West Virginia University, Morgantown, West Virginia, United States.
authors.forename: Visvanathan
authors.initials: V
authors.lastname: Ramamurthy
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000429:Alcohol Oxidoreductases; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010750:Phosphoproteins / Q000378:metabolism; D012164:Retinal Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D055351:Retinal Neurons / Q000378:metabolism* / Q000473:pathology; D013570:Synaptic Membranes / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C498604:Aipl1 protein, mouse; D015415:Biomarkers; D056970:Co-Repressor Proteins; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D000429:Alcohol Oxidoreductases; C111341:Ctbp2 protein, mouse
keywords: LCA; childhood blindness; photoreceptor degeneration; remodeling; retina
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