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Xianfang Rong, Xiaofen Mo, Jingyan Dong, School of Pharmacy, Shanghai Jiao Tong University; Prolonged Neuroprotective Effect Of Erythropoietin-loaded Dextran Microparticles Based Plga/pla Microspheres On Retinal Ganglion Cells In Optic Nerve Rats. Invest. Ophthalmol. Vis. Sci. 2011;52(14):475.
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To explore the neuroprotective effect of erythropoietin-loaded dextran microparticles based Poly (DL-lactide-co-glycolide)/ Poly (DL-lacide) (PLGA/PLA) microspheres (EPO-loaded PLGA/PLA microspheres) on the injured retinal ganglion cells (RGCs) in optic nerve crush rats for a prolonged period of time.
EPO-loaded PLGA/PLA microspheres were first prepared by a novel technique "aqueous-aqueous emulsion", and in votro EPO release profile was assessed. Bioactive effect of EPO released from the PLGA/PLA microspheres was explored in votro on the retinal explants in three-dimensional culture system. The density and length of neurite outgrowth of the explants were calculated when cultured for 6 days. Lastly, neuroprotective effect of EPO-loaded PLGA/PLA microspheres on RGCs was evaluated in optic nerve crush rats when compared with EPO protein solution. After single intravitreal administration of EPO-loaded microspheres or weekly injections of EPO, TUNEL staining of apoptotic RGCs, DiI retrograde labeling of survival RGCs were performed at different time pos-crush until 8 weeks.
The results demonstrated that sustained release of EPO from PLGA/PLA microspheres could last for at least 60 days. EPO released from PLGA/PLA microspheres showed efficaciously neuroregenerative effect on retinal explants. Both TUNEL staining and DiI retrograde labeling revealed that EPO-loaded PLGA/PLA microspheres were neuroprotective on RGCs for 8 weeks.
Single intravitreal injection of EPO-loaded PLGA/PLA microspheres appears to have a prolonged protective effect on RGCs in optic nerve crush rats. The PLGA/PLA microspheres may be a feasible protein drug delivery system including EPO for retinal degeneration diseases.
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