PPARβ/δ selectively regulates phenotypic features of age-related macular degeneration
Open accessAbstract
Peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) is a nuclear receptor that regulates differentiation, inflammation, lipid metabolism, extracellular matrix remodeling, and angiogenesis in multiple tissues. These pathways are also central to the pathogenesis of age-related macular degeneration (AMD), the leading cause of vision loss globally. With the goal of identifying signaling pathways that may be important in the development of AMD, we investigated the impact of PPARβ/δ activation on ocular tissues affected in the disease. PPARβ/δ is expressed and can be activated in AMD vulnerable cells, including retinal pigment epithelial (RPE) and choroidal endothelial cells. Further, PPARβ/δ knockdown modulates AMD-related pathways selectively. Specifically, genetic ablation of Pparβ/δ in aged mice resulted in exacerbation of several phenotypic features of early dry AMD, but attenuation of experimentally induced choroidal neovascular (CNV) lesions. Antagonizing PPARβ/δ in both in vitro angiogenesis assays and in the in vivo experimentally induced CNV model, inhibited angiogenesis and angiogenic pathways, while ligand activation of PPARβ/δ, in vitro, decreased RPE lipid accumulation, characteristic of dry AMD. This study demonstrates for the first time, selective regulation of a nuclear receptor in the eye and establishes that selective targeting of PPARβ/δ may be a suitable strategy for treatment of different clinical sub-types of AMD.
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Some features of dry AMD were recapitulated in Pex11β−/− mice, such as increased accumulation of sub-RPE deposits and accumulation of lipofuscin.
“Some features of dry AMD were recapitulated in Pex11β−/− mice, such as increased accumulation of sub-RPE deposits and accumulation of lipofuscin (Choudhary et al., 2016).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Choudhary et al., 2016
PPARβ/δ is implicated in modification of AMD disease severity, but distinct effects of PPARβ/δ modulation depend on cell type.
“Recently PPARβ/δ was implicated in modification of AMD disease severity, but distinct effects of PPARβ/δ modulation depended on cell type (Choudhary et al., 2016).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Choudhary et al., 2016
PPAR activity in RPE cells modulates expression of extracellular matrix-related genes and genes involved in lipid metabolism such as APOE, APOA, and LDLR.
“PPAR activity in RPE cells in this study was found to modulate expression of extracellular matrix-related genes and genes involved in lipid metabolism such as apolipoprotein E (APOE), apolipoprotein A (APOA), and low-density lipoprotein receptor (LDLR).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Choudhary et al., 2016
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Investigating the Role of PPARβ/δ in Retinal Vascular Remodeling Using Pparβ/δ-Deficient Mice
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Self-citationPhysiology and Pathophysiology of PPARs in the Eye
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- Authors
- Choudhary, M., Ding, J.-D., Qi, X., Boulton, M. E., Yao, P.-L., Peters, J. M., & Malek, G.
- Affiliations
- Duke University (US)
- Department of Ophthalmology, Duke University School of Medicine, Durham, NC 27703, USA
- Indiana University School of Medicine (US)
- Pennsylvania State University (US)
- Corresponding author
- Malek, Goldis
- Venue
- Aging
- Publisher
- Impact Journals, LLC
- Published
- 2016-09-08
- Volume
- 8
- Issue
- 9
- Pages
- 1952-1978
- ISSN
- 1945-4589 (ISSN-L)
- PMC
- PMC5076447
- OpenAlex
- W2519280196
- Cited by
- 39
- References
- 67
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2022: 8 · 2021: 6 · 2020: 11 · 2018: 6
- FWCI
- 2.12
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Aging (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Purdue University Indianapolis (Indiana University) (submittedVersion, cc-by)
- Publisher
- Funders
- National Eye Institute (R01EY020868, P30EY005722)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- PPARδ, age-related macular degeneration, dry age-related macular degeneration, choroidal neovascularization, angiogenesis, retinal pigment epithelium, choroidal endothelial cells, lipid accumulation, nuclear receptor signaling, ocular aging
- MeSH terms
- Aged, Animals, Cell Line, Cell Movement, Cell Survival, Electroretinography, Female, Humans, Macaca mulatta, Macular Degeneration, Male, Mice, Transgenic, Middle Aged, Neovascularization, Pathologic, Phenols, Phenotype, Sulfhydryl Compounds, Sulfones, Thiazoles, Thiophenes, Signal Transduction, PPAR-beta, Mice, Retinal Pigment Epithelium, Young Adult
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