title: Effects of erythropoietin-dextran microparticle-based PLGA/PLA microspheres on RGCs.
abstract: OBJECTIVE
  We explored the neuroprotective effects of erythropoietin (EPO)-loaded dextran microparticle-based Poly(DL-lactide-co-glycolide)/Poly(DL-lactide) (PLGA/PLA) microspheres (EPO-dextran PLGA/PLA microspheres) on retinal ganglion cells (RGCs) in optic nerve crush rats for a prolonged period of time.
  
  
  METHODS
  EPO-dextran PLGA/PLA microspheres were prepared first by a novel solid-in-oil-in-water (S/O/W) technique. Then, the in vitro EPO release profile was assessed. Afterward, the bioactive effect of EPO released from EPO-dextran PLGA/PLA microspheres was explored in vitro on the retinal explants. Lastly, the neuroprotective effects of EPO-dextran PLGA/PLA microspheres on RGCs were evaluated in optic nerve crush rats with TUNEL staining for apoptotic RGCs. The level of glial fibrillary acidic protein (GFAP) expressed in retina was explored by immunohistochemistry staining. Survival RGCs were observed by DiI retrograde labeling using a DiI fluorescent tracer (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate).
  
  
  RESULTS
  The results demonstrated that a sustained release of EPO from PLGA/PLA microspheres could last for at least 60 days. EPO released from the microspheres showed as efficaciously neuroregenerative as EPO protein solution on retinal explants (P = 0.2554 for neurite density, P = 0.1004 for neurite length). TUNEL staining revealed that EPO-dextran PLGA/PLA microspheres remarkably reduced RGCs death when compared to the control (untreated) group (P < 0.01 at five days and one week post-crush, P < 0.05 at two weeks post-crush). Increased GFAP expression in retina was reduced greatly in EPO-dextran PLGA/PLA microspheres-administrated rats two weeks post optic nerve crush. DiI retrograde labeling revealed that a single injection of EPO-dextran PLGA/PLA microspheres significantly promoted RGCs survival (P < 0.01 at four and eight weeks post-crush).
  
  
  CONCLUSIONS
  A single intravitreal injection of EPO-dextran PLGA/PLA microspheres appeared to have a prolonged protective effect on RGCs in optic nerve crush rats. The PLGA/PLA microspheres may be a feasible protein delivery system, such as EPO, to intravitreal injection for retinal degeneration diseases.
authors.affiliation: Department of Ophthalmology and Vision Science, Eye and ENT Hospital, Institute of Brain Science and State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Xianfang
authors.initials: X
authors.lastname: Rong
authors.forename: Sixing
authors.initials: S
authors.lastname: Yang
authors.forename: Huamao
authors.initials: H
authors.lastname: Miao
authors.forename: Tingting
authors.initials: T
authors.lastname: Guo
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Wang
authors.forename: Wanru
authors.initials: W
authors.lastname: Shi
authors.forename: Xiaofen
authors.initials: X
authors.lastname: Mo
authors.forename: Weien
authors.initials: W
authors.lastname: Yuan
authors.forename: Tuo
authors.initials: T
authors.lastname: Jin
mesh_terms: D000818:Animals; D017209:Apoptosis; D001672:Biocompatible Materials / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003692:Delayed-Action Preparations; D003911:Dextrans / Q000494:pharmacology*; D004195:Disease Models, Animal; D004337:Drug Carriers; D004339:Drug Compounding; D004921:Erythropoietin / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019344:Lactic Acid / Q000494:pharmacology*; D008297:Male; D008863:Microspheres; D011100:Polyglycolic Acid / Q000494:pharmacology*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D012162:Retinal Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D003911:Dextrans; D004337:Drug Carriers; D005904:Glial Fibrillary Acidic Protein; D004921:Erythropoietin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid