June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
PEDF-derived Peptides delay Photoreceptor Cell Death in two Experimental Models of Retinitis Pigmentosa.
Author Affiliations & Notes
  • Alberto M Hernandez-Pinto
    Centro de Investigaciones Biológicas, Madrid, Spain
  • Preeti Subramanian
    National Eye Institute, Bethesda, MD
  • Federica Polato
    National Eye Institute, Bethesda, MD
  • Andrés de la Rocha
    Centro de Investigaciones Biológicas, Madrid, Spain
  • Enrique J De La Rosa
    Centro de Investigaciones Biológicas, Madrid, Spain
  • Patricia Becerra
    National Eye Institute, Bethesda, MD
  • Footnotes
    Commercial Relationships Alberto Hernandez-Pinto, None; Preeti Subramanian, None; Federica Polato, None; Andrés de la Rocha, None; Enrique De La Rosa, None; Patricia Becerra, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 5413. doi:
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      Alberto M Hernandez-Pinto, Preeti Subramanian, Federica Polato, Andrés de la Rocha, Enrique J De La Rosa, Patricia Becerra; PEDF-derived Peptides delay Photoreceptor Cell Death in two Experimental Models of Retinitis Pigmentosa.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5413.

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

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Abstract

Purpose: Pigment epithelium-derived factor (PEDF) is a 50 kDa glycoprotein with neuroprotective, anti-angiogenic, and immunomodulatory activities. PEDF-R is a critical receptor for the PEDF cytoprotective activities. PEDF levels decrease in several retinopathies, including Retinitis Pigmentosa (RP), a heterogeneous group of hereditary retinal dystrophies characterized by progressive loss of vision due to photoreceptor cell death. Retinal degeneration 10 (rd10) mice are a model of autosomal recessive RP. These mice carry a spontaneous mutation of the rod-phosphodiesterase (PDE6) gene, leading to a rod degeneration. The aim of the present work is to study the role of PEDF receptor-effector system in rd10 mice.

Methods: Retinas from rd10 and wild type (WT) mice were used. Western blotting of retina extracts using anti-PEDF-R was performed. Rd10 retina explants were dissected and cultured to assess PEDF protection “ex-vivo”. WT retina explants were cultured for 72 hours in presence of zaprinast (a PDE6 inhibitor). A set of PEDF-derived peptides were chemically synthesized (34-mer, 44-mer, 17-mer and blocking peptide P1) and recombinant human PEDF was purified from conditioned media of BHK cells with PEDF expression vectors. TUNEL assay was performed to evaluate photoreceptor cell death after culture.

Results: The levels of PEDF-R were higher in retina extracts of rd10 than of wild type. PEDF decreased the number of apoptotic photoreceptor in rd10 retina explants relative to those in untreated cultures. Zaprinast treatment increased the number of apoptotic photoreceptor cells in WT retinal explants. PEDF, 44-mer or 17-mer clearly attenuated photoreceptor cell death induced by zaprinast in WT retina explants. Additions in excess over ligand of P1, a peptide that blocks the PEDF/PEDF-R interactions, impaired the rescue mediated by PEDF, 44mer and 17mer.

Conclusions: PEDF fragments delay photoreceptor degeneration in retinas of experimental models of inherited RP. The data implies that the PEDF receptor-effector system might be involved in RP physiopathology and may constitute a therapeutic target.

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