title: Deletion of aryl hydrocarbon receptor AHR in mice leads to subretinal accumulation of microglia and RPE atrophy.
abstract: OBJECTIVE
  The aryl hydrocarbon receptor (AHR) is a ligand-activated nuclear receptor that regulates cellular response to environmental signals, including UV and blue wavelength light. This study was undertaken to elucidate AHR function in retinal homeostasis.
  
  
  METHODS
  RNA-seq data sets were examined for Ahr expression in the mouse retina and rod photoreceptors. The Ahr(-/-) mice were evaluated by fundus imaging, optical coherence tomography, histology, immunohistochemistry, and ERG. For light damage experiments, adult mice were exposed to 14,000 to 15,000 lux of diffuse white light for 2 hours.
  
  
  RESULTS
  In mouse retina, Ahr transcripts were upregulated during development, with continued increase in aging rod photoreceptors. Fundus examination of 3-month-old Ahr(-/-) mice revealed subretinal autofluorescent spots, which increased in number with age and following acute light exposure. Ahr(-/-) retina also showed subretinal microglia accumulation that correlated with autofluorescence changes, RPE abnormalities, and reactivity against immunoglobulin, complement factor H, and glial fibrillary acidic protein. Functionally, Ahr(-/-) mice displayed reduced ERG c-wave amplitudes.
  
  
  CONCLUSIONS
  The Ahr(-/-) mice exhibited subretinal accumulation of microglia and focal RPE atrophy, phenotypes observed in AMD. Together with a recently published report on another Ahr(-/-) mouse model, our study suggests that AHR has a protective role in the retina as an environmental stress sensor. As such, its altered function may contribute to human AMD progression and provide a target for pharmacological intervention.
authors.affiliation: Neurobiology-Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Soo-Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Neurobiology-Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: Yang
authors.affiliation: Neurobiology-Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States Department of Ophthalmology, National Cheng Kung University and Hospital, Tainan, Taiwan.
authors.forename: Yi-Sheng
authors.initials: YS
authors.lastname: Chang
authors.affiliation: Neurobiology-Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Jung-Woong
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Neurobiology-Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Matthew
authors.initials: M
authors.lastname: Brooks
authors.affiliation: Division of Epidemiology and Clinical Application, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Emily Y
authors.initials: EY
authors.lastname: Chew
authors.affiliation: Section on Neuron-Glia Interactions in Retinal Disease, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Wai T
authors.initials: WT
authors.lastname: Wong
authors.affiliation: Imaging Core, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Fariss
authors.affiliation: Neurobiology-Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Rivka A
authors.initials: RA
authors.lastname: Rachel
authors.affiliation: Neurobiology-Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Cogliati
authors.affiliation: Visual Function Core, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Haohua
authors.initials: H
authors.lastname: Qian
authors.affiliation: Neurobiology-Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Anand
authors.initials: A
authors.lastname: Swaroop
mesh_terms: D000818:Animals; D001284:Atrophy / Q000378:metabolism / Q000473:pathology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D005654:Fundus Oculi; D017353:Gene Deletion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D055213:Retinal Pigment Epithelium / Q000378:metabolism* / Q000473:pathology; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism* / Q000473:pathology; D012173:Retinitis / Q000378:metabolism / Q000473:pathology; D041623:Tomography, Optical Coherence; D059467:Transcriptome
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018336:Receptors, Aryl Hydrocarbon; C484722:Ahr protein, mouse
keywords: RPE atrophy; microglia; orphan nuclear receptor; retinal degeneration; subretinal deposits