Deletion of aryl hydrocarbon receptor AHR in mice leads to subretinal accumulation of microglia and RPE atrophy

Soo Young Kim, Hyun Jin Yang, Yi Sheng Chang, Jung Woong Kim, Matthew Brooks, Emily Y. Chew, Wai T. Wong, Robert N. Fariss, Rivka A. Rachel, Tiziana Cogliati, Haohua Qian, Anand Swaroop

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Abstract

PURPOSE. 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.

Original languageEnglish
Pages (from-to)6031-6040
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume55
Issue number9
DOIs
Publication statusPublished - 2014

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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    Kim, S. Y., Yang, H. J., Chang, Y. S., Kim, J. W., Brooks, M., Chew, E. Y., Wong, W. T., Fariss, R. N., Rachel, R. A., Cogliati, T., Qian, H., & Swaroop, A. (2014). Deletion of aryl hydrocarbon receptor AHR in mice leads to subretinal accumulation of microglia and RPE atrophy. Investigative Ophthalmology and Visual Science, 55(9), 6031-6040. https://doi.org/10.1167/iovs.14-15091