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H. Li, C.J. Barnstable, J. Tombran–Tink; Small Pedf Peptides Encapsulated in Controlled Release Poly (Lactic–co–Glycolic) Acid Microspheres Protect Retinal Ganglion Cells From Transient Ischemic Injury . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1564.
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© ARVO (1962-2015); The Authors (2016-present)
To assess the ability of N–terminal peptide fragments of PEDF encapsulated in biodegradable PLGA (poly lactic–co–glycolic acid) microspheres to protect the retina against ischemic injury.
All experiments in this study adhered to ARVO guidelines and were approved by the IACUC. Transient retinal ischemia was induced in C57/B6 mice by elevating the IOP to 120 mmHg for 60 min in one eye. Contralateral eyes served as controls. Ischemia was immediately followed by intravitreal injections of microspheres (MS) with a mean size of 200nm that encapsulated PEDF76–95, PEDF 91–110, PEDF106–125, or the control PEDF136–155 peptides. Animals were sacrificed 7d after ischemia was induced. Eyes were fixed in paraformaldehyde, embedded in paraffin and sectioned at 5µm. Damage was assessed morphologically using H&E stained sections. The thickness of the inner nuclear layer (INL) and inner plexiform layer (IPL) was analyzed and cells were counted to determine changes in the retinal ganglion cell (RGC) layer.
, The INL thickness was preserved by 45.09% more in PEDF76–95 MS injected group (p<0.01) compared to eyes injected with the control PEDF peptide. PEDF 91–110 and PEDF106–125 MS injections did not show significant protection of the INL. PEDF76–95 and PEDF91–110 MS injections showed 25.46% and 12.16% preservation of the IPL but this did not reach the statistical significance. PEDF76–95 and PEDF91–110 MS injections resulted in a 21.57% and 47.23% (p<0.01) respectively, increase in the living number of RGCs compared to the control peptide. There was no significant protection of cells in the ganglion cell layer with PEDF106–125 MS injections.
These studies have identified a small surface epitope on the PEDF molecule that mediates protection from cell death induced by transient ischemia and have shown that such peptides can be readily delivered to the eye in therapeutic doses using a slow release microencapsulation system. Supported by the David Woods Kemper Memorial Foundation, the NIH, RPB Inc., and the Connecticut Lions.
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