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Neuroprotective activity of Pigment Epithelium-derived Factor derived therapeutics

Wednesday, November 06, 2013 — Poster Session I

4:00 p.m. – 6:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • JD Kenealey
  • P Subramanian
  • SP Becerra


Age related macular degeneration (AMD), glaucoma, and diabetic retinopathy are neurodegenerative ocular pathologies that can lead to irreversible blindness. Currently, there is no direct treatment that protects retinal neurons in these pathologies from cell death. Pigment epithelium-derived factor (PEDF) is a non-inhibitory serpin that has been shown to prevent retinal cell death in both in vitro and animal models. PEDF’s neuroprotective activity is stimulated by an interaction with the exodomain of the PEDF-Receptor (PEDF-R). However, the structural components of PEDF required for neuroprotective activity have not been elucidated. This study defines the molecular determinants for the neuroprotective activity of PEDF by utilizing PEDF derived molecules. We show that binding to PEDF-R and the neuroprotective activity of PEDF are contained in a 17 amino acid region. Additionally, alanine substitutions within this region result in molecules with both lower and higher affinity for PEDF-R, and altered neuroprotective activity. This study identifies a novel neuroprotective region and delineates the molecular interactions required for activity.

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