September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Investigating the role of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in wet age-related macular degeneration (AMD)
Author Affiliations & Notes
  • Mayur Choudhary
    Ophthalmology, Duke Eye Center, Durham, North Carolina, United States
  • Jeffrey Peters
    Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, Pennsylvania, United States
  • Goldis Malek
    Ophthalmology, Duke Eye Center, Durham, North Carolina, United States
  • Footnotes
    Commercial Relationships   Mayur Choudhary, None; Jeffrey Peters, None; Goldis Malek, None
  • Footnotes
    Support  NEI EY02868 (GM), NIH P30 EY005722 (Duke Eye Center) and RPB core grant (Duke eye center)
Investigative Ophthalmology & Visual Science September 2016, Vol.57, No Pagination Specified. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Mayur Choudhary, Jeffrey Peters, Goldis Malek; Investigating the role of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in wet age-related macular degeneration (AMD). Invest. Ophthalmol. Vis. Sci. 2016;57(12):No Pagination Specified.

      Download citation file:

      © ARVO (1962-2015); The Authors (2016-present)

  • Supplements

Purpose : The majority of AMD-related severe vision loss occurs in patients with the wet form of the disease. It is characterized by pathological neovascularization from the choriocapillaris. Given only a fraction of AMD patients demonstrate benefit with the current anti-VEGF therapies, it is crucial to identify other pathogenic mechanisms involved in neovascularization. PPARs are members of a family of lipid activated nuclear receptors. Since the PPARβ/δ isoform has been shown to regulate angiogenesis and inflammation, we investigated its role in wet AMD.

Methods : Cell migration and tube formation in RF/6A (macaque choroidal endothelial) cells were analyzed after PPARβ/δ knockdown, ligand (agonist or antagonist) treatment, and incubation with conditioned media (CM) from ARPE19 (human retinal pigment epithelium) cells treated with PPARβ/δ ligands. The choroid was examined in eyes from aged Pparβ/δ-/- and Pparβ/δ+/+ mice by electron microscopy. The effect of PPARβ/δ expression (Pparβ/δ-/- and Pparβ/δ+/+) and pharmacological modulation [vehicle control, PPARβ/δ antagonist (GSK0660) or PPARβ/δ agonist (GW0742)] on choroidal neovascular (CNV) lesion severity was examined in isolectin-IB4 stained flatmounts of mouse eyes following laser induced CNV. Cryosections from Pparβ/δ-/- and Pparβ/δ+/+ eyes were probed with antibodies to Iba1 and F4/80, to evaluate microglial localization within the CNV lesions.

Results : Knocking down PPARβ/δ expression with siRNA or antagonizing PPARβ/δ function decreased bFGF-induced cell migration and tube formation. Additionally, treatment of ARPE19 CM with a PPARβ/δ antagonist was able to reverse CM-induced migration of RF/6A cells. While ultrastructural images displayed no differences in the choroid between Pparβ/δ-/- and Pparβ/δ+/+controls, Pparβ/δ-/- mice exhibited decreased volume and size of CNV lesions and a 2-fold higher localization of Iba1+ and F4/80+ microglia as compared to age-matched controls.

Conclusions : These results support our previous findings that PPARβ/δ regulates AMD pathobiology in a cell-specific manner. While PPARβ/δ antagonism may have therapeutic benefit in the context of the choroid and wet-AMD, RPE cells might benefit from ligand activation of PPARβ/δ to treat sub-RPE deposit formation. Finally, the increase in microglial cells within smaller CNV lesions may be indicative of macrophage polarization regulated by PPARβ/δ.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.


This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.