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PPARβ/δ selectively regulates phenotypic features of age-related macular degeneration.

Publication ,  Journal Article
Choudhary, M; Ding, J-D; Qi, X; Boulton, ME; Yao, P-L; Peters, JM; Malek, G
Published in: Aging (Albany NY)
September 8, 2016

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.

Duke Scholars

Published In

Aging (Albany NY)

DOI

EISSN

1945-4589

Publication Date

September 8, 2016

Volume

8

Issue

9

Start / End Page

1952 / 1978

Location

United States

Related Subject Headings

  • Young Adult
  • Thiophenes
  • Thiazoles
  • Sulfones
  • Signal Transduction
  • Retinal Pigment Epithelium
  • Phenotype
  • PPAR-beta
  • Neovascularization, Pathologic
  • Middle Aged
 

Citation

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Choudhary, M., Ding, J.-D., Qi, X., Boulton, M. E., Yao, P.-L., Peters, J. M., & Malek, G. (2016). PPARβ/δ selectively regulates phenotypic features of age-related macular degeneration. Aging (Albany NY), 8(9), 1952–1978. https://doi.org/10.18632/aging.101031
Choudhary, Mayur, Jin-Dong Ding, Xiaoping Qi, Michael E. Boulton, Pei-Li Yao, Jeffrey M. Peters, and Goldis Malek. “PPARβ/δ selectively regulates phenotypic features of age-related macular degeneration.Aging (Albany NY) 8, no. 9 (September 8, 2016): 1952–78. https://doi.org/10.18632/aging.101031.
Choudhary M, Ding J-D, Qi X, Boulton ME, Yao P-L, Peters JM, et al. PPARβ/δ selectively regulates phenotypic features of age-related macular degeneration. Aging (Albany NY). 2016 Sep 8;8(9):1952–78.
Choudhary, Mayur, et al. “PPARβ/δ selectively regulates phenotypic features of age-related macular degeneration.Aging (Albany NY), vol. 8, no. 9, Sept. 2016, pp. 1952–78. Pubmed, doi:10.18632/aging.101031.
Choudhary M, Ding J-D, Qi X, Boulton ME, Yao P-L, Peters JM, Malek G. PPARβ/δ selectively regulates phenotypic features of age-related macular degeneration. Aging (Albany NY). 2016 Sep 8;8(9):1952–1978.

Published In

Aging (Albany NY)

DOI

EISSN

1945-4589

Publication Date

September 8, 2016

Volume

8

Issue

9

Start / End Page

1952 / 1978

Location

United States

Related Subject Headings

  • Young Adult
  • Thiophenes
  • Thiazoles
  • Sulfones
  • Signal Transduction
  • Retinal Pigment Epithelium
  • Phenotype
  • PPAR-beta
  • Neovascularization, Pathologic
  • Middle Aged