TY - JOUR
T1 - A PEDF N-terminal peptide protects the retina from ischemic injury when delivered in PLGA nanospheres
AU - Li, Hong
AU - Tran, Veronique V.
AU - Hu, Yueyue
AU - Mark Saltzman, W.
AU - Barnstable, Colin J.
AU - Tombran-Tink, Joyce
N1 - Funding Information:
This work was supported by NIH grant EY13865, Research to Prevent Blindness, Inc., The David Woods Kemper Memorial Foundation, and The Connecticut Lions Eye Research Foundation. We would like to thank Dr. Caroline Zeiss for assistance with the morphometric analysis, Dr. Ron Adelman for use of his animal surgery suite, Dr. Samuel Shao-Min Zhang for assistance with figure preparation, and Dr. Mugen Liu, Dr. Yan Luo, Stephen Viviano and Michael Schadt for technical assistance.
PY - 2006/10
Y1 - 2006/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33747874701&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33747874701&partnerID=8YFLogxK
U2 - 10.1016/j.exer.2006.04.014
DO - 10.1016/j.exer.2006.04.014
M3 - Article
C2 - 16822505
AN - SCOPUS:33747874701
VL - 83
SP - 824
EP - 833
JO - Experimental Eye Research
JF - Experimental Eye Research
SN - 0014-4835
IS - 4
ER -