Small Retinoprotective Peptides Reveal a Receptor-binding Region on Pigment Epithelium-derived Factor

Abstract

Background: Pigment epithelium-derived factor (PEDF) interacts with its receptor PEDF-R to exert cytoprotection. Results: Alanine scanning of a small fragment (17-mer) of PEDF reveals key interacting residues for binding PEDF-R and alternative retinoprotective peptide versions with higher efficacy. Conclusion: The 17-mer contains a novel PEDF-R binding region important for retinoprotection. Significance: Altered PEDF peptides could be exploited pharmacologically to improve protection of photoreceptors from degeneration.

PEDF plus DHA modulate inflammation and stimulate nerve regeneration after HSV-1 infection

“…In the present study, there was also a decrease in corneal neovascularization that could be due to the antiangiogenic portion of the glycoprotein, the 34-mer-PEDF (Barnstable and Tombran-Tink, 2004; Becerra, 2008; Kenealey et al, 2015). It has been shown that PEDF blocks the survival, proliferation and migration of vascular endothelial cells by disrupting the pro-angiogenic action of vascular endothelial factor (VEGF), suppressing the expression of metalloproteinases (MMPs)-2 and-9 and upregulating Fas/Fas ligand (Haurigot et al, 2012; Matsui et al, 2012, Volpert et al, 2002).…”

“…It appears to act through different receptors, including a PEDF receptor (PEDF-R), which has been shown to interact with the N-terminal portion of the PEDF molecule, mediating its neurotrophic effect and neuronal differentiating activity (Kenealey et al, 2015; Notari et al, 2006; Subramanian et al, 2010). Although the mechanism by which PEDF+DHA promotes nerve regeneration in the rabbit is not completely understood, we have previously found that corneal epithelial cells express a PEDF-R linked to phospholipase activity and that the peptide 44-mer-PEDF (which has neurotrophic properties), in conjunction with DHA, also increases corneal nerve regeneration (He et al, 2015).…”

Potential of Müller Glia for Retina Neuroprotection

“…65 The neuroprotective effect of PEDF has been demonstrated by observations that injection of PEDF protein peptides into the eye of the C3H/HeN retinal degeneration 1 (rd1) mouse confers strong neuroprotection to degenerating photoreceptors. 66 This rescue from photoreceptor cell death has been attributed to a decrease in intracellular Ca 2+ concentrations and consequently to a decrease in calpain activity induced by PEDF. 67 Further confirmation of the neurotrophic effects of PEDF has been shown by inhibition of photoreceptor apoptosis following lentivirus-mediated retinal gene transfer of PEDF into the subretinal space of the RCS rat.…”

Pigment Epithelium-Derived Factor (PEDF) Fragments Prevent Mouse Cone Photoreceptor Cell Loss Induced by Focal Phototoxicity In Vivo

“…PEDF-R is distributed in the inner segments of photoreceptors [ 21 , 29 ]. Small PEDF peptides from the neurotrophic domain bind PEDF-R and exhibit survival activities on retinal cells [ 21 , 23 , 31 ]. In this regard, the protective capacity of 17-mer (a peptide of 17 amino acids spanning positions 98–114 of the human PEDF sequence), and 17-mer[H105A] (a derived 17-mer peptide with single residue substitution to alanine on position 105 and improved retinoprotective activity) has been recently described in vivo and ex vivo in the rd1 , rd10 and Mitf mouse models of inherited genetic retinal degeneration [ 21 , 23 , 32 ].…”