Deletion of aryl hydrocarbon receptor AHR in mice leads to subretinal accumulation of microglia and RPE atrophy.
Open accessAbstract
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.
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The increased Iba positive cells in the inner retina may represent migrating activated microglia.
“and may represent migrating activated microglia (Kim et al., 2014).”
From Microtubule-associated protein 1 light chain 3B, (LC3B) is necessary to maintain lipid-mediated homeostasis in the retinal pigment epithelium (2018) · cites this paper as Kim et al., 2014
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- Authors
- 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.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Kim, Soo-Young
- Swaroop, Anand
- ORCID
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2014-09-24
- Volume
- 55
- Issue
- 9
- Pages
- 6031
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- PMC
- PMC4176417
- OpenAlex
- W2069765448
- Cited by
- 72
- References
- 64
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 8 · 2023: 2 · 2022: 8 · 2021: 10 · 2020: 10 · 2019: 5 · 2018: 7 · 2017: 4 · 2016: 6 · 2015: 8
- FWCI
- 5.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Investigative Ophthalmology & Visual Science (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Eye Institute
- National Cancer Institute
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Keywords
- aryl hydrocarbon receptor, AhR knockout mice, retinal pigment epithelium atrophy, age-related macular degeneration, rod photoreceptors, light-induced retinal damage, retinal homeostasis, complement factor H, glial fibrillary acidic protein
- MeSH terms
- Animals, Atrophy, Disease Models, Animal, Fundus Oculi, Mice, Inbred C57BL, Retinal Degeneration, Retinitis, Gene Deletion, Microglia, Retinal Rod Photoreceptor Cells, Receptors, Aryl Hydrocarbon, Mice, Knockout, Tomography, Optical Coherence, Mice, Basic Helix-Loop-Helix Proteins, Retinal Pigment Epithelium, Transcriptome
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