A PEDF N-terminal peptide protects the retina from ischemic injury when delivered in PLGA nanospheres

Hong Li, Veronique V. Tran, Yueyue Hu, W. Mark Saltzman, Colin J. Barnstable, Joyce Tombran-Tink

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

The neuroprotective effects of small pigment epithelium-derived factor (PEDF) peptides injected intravitreally as free peptides or delivered in poly(lactide-co-glycolide) (PLGA) nanospheres, were tested in retinal ischemic injury. We induced transient ischemia in C57BL/6 mice by elevating the intraocular pressure to the equivalent of 120 mmHg for 60 min, then injected these eyes with one of the following: PBS, full-length native PEDF, N-terminal peptides-PEDF136-155 and PEDF82-121, blank PLGA nanospheres or PLGA loaded with PEDF82-121 (PLGA-PEDF82-121). Morphometric analysis and TUNEL assays were used to determine the extent of retinal damage. Transient ischemia caused a rapid reduction in the number of viable cells in the retinal ganglion cell (RGC) layer over 48 h as compared to non-ischemic retinas. About 76% surviving cells in the RGC layer were observed in the full-length PEDF protein treated group, whereas only 32% of cells survived in the PBS group. Thus, PEDF prevented approximately 44% of the cell death in the RGC layer resulting from transient ischemia. PEDF82-121 peptide was as effective as full-length PEDF when injected as either a free peptide or delivered in PLGA nanospheres. PLGA-PEDF82-121 showed longer-term protection of the RGC layer with no noticeable side effects at 7 days. PEDF and PEDF82-121 lessened damage to the IPL as measured by layer thickness. PEDF and PEDF82-121 also delayed retinal responses to ischemic injury as measured by GFAP immunolabeling in Müller cells. PEDF82-121 is an effective neuroprotective peptide in retinal ischemia. PLGA-PEDF82-121 offers greater protection to the retina suggesting that this peptide and the method of delivering therapeutically active drugs have potential clinical advantages for longer-term treatments of retinal diseases.

Original languageEnglish (US)
Pages (from-to)824-833
Number of pages10
JournalExperimental Eye Research
Volume83
Issue number4
DOIs
StatePublished - Oct 1 2006

Fingerprint

Nanospheres
Retina
Retinal Ganglion Cells
Peptides
Wounds and Injuries
Ischemia
Polyglactin 910
Retinal Diseases
In Situ Nick-End Labeling
Neuroprotective Agents
polylactic acid-polyglycolic acid copolymer
pigment epithelium-derived factor
Intraocular Pressure
Inbred C57BL Mouse
Cell Death
Cell Count

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

@article{93106c5b262146618a2b6d78ad43dbc2,
title = "A PEDF N-terminal peptide protects the retina from ischemic injury when delivered in PLGA nanospheres",
abstract = "The neuroprotective effects of small pigment epithelium-derived factor (PEDF) peptides injected intravitreally as free peptides or delivered in poly(lactide-co-glycolide) (PLGA) nanospheres, were tested in retinal ischemic injury. We induced transient ischemia in C57BL/6 mice by elevating the intraocular pressure to the equivalent of 120 mmHg for 60 min, then injected these eyes with one of the following: PBS, full-length native PEDF, N-terminal peptides-PEDF136-155 and PEDF82-121, blank PLGA nanospheres or PLGA loaded with PEDF82-121 (PLGA-PEDF82-121). Morphometric analysis and TUNEL assays were used to determine the extent of retinal damage. Transient ischemia caused a rapid reduction in the number of viable cells in the retinal ganglion cell (RGC) layer over 48 h as compared to non-ischemic retinas. About 76{\%} surviving cells in the RGC layer were observed in the full-length PEDF protein treated group, whereas only 32{\%} of cells survived in the PBS group. Thus, PEDF prevented approximately 44{\%} of the cell death in the RGC layer resulting from transient ischemia. PEDF82-121 peptide was as effective as full-length PEDF when injected as either a free peptide or delivered in PLGA nanospheres. PLGA-PEDF82-121 showed longer-term protection of the RGC layer with no noticeable side effects at 7 days. PEDF and PEDF82-121 lessened damage to the IPL as measured by layer thickness. PEDF and PEDF82-121 also delayed retinal responses to ischemic injury as measured by GFAP immunolabeling in M{\"u}ller cells. PEDF82-121 is an effective neuroprotective peptide in retinal ischemia. PLGA-PEDF82-121 offers greater protection to the retina suggesting that this peptide and the method of delivering therapeutically active drugs have potential clinical advantages for longer-term treatments of retinal diseases.",
author = "Hong Li and Tran, {Veronique V.} and Yueyue Hu and {Mark Saltzman}, W. and Barnstable, {Colin J.} and Joyce Tombran-Tink",
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A PEDF N-terminal peptide protects the retina from ischemic injury when delivered in PLGA nanospheres. / Li, Hong; Tran, Veronique V.; Hu, Yueyue; Mark Saltzman, W.; Barnstable, Colin J.; Tombran-Tink, Joyce.

In: Experimental Eye Research, Vol. 83, No. 4, 01.10.2006, p. 824-833.

Research output: Contribution to journalArticle

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AU - Tran, Veronique V.

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