The Toxic Effect Observation Of The Retina After Vitreous Chamber Injected With PDGF-a Receptor Antisense Oligonucleotide

Objective：To explore the toxic effect of PDGF-a receptor antisenseoligonucleotides on the retina.Methods:24healthy adult colored rabbits were selected,and randomlydivided into four groups.each group had six.PDGF-a receptor antisenseoligonucleotides and liposome were mixed together with the ratio(W/V)of1:2.5, then let the proportioning concentration stand at the roomtemperature for30min. vitreous chamber of the right eye was injectedwith0.1ml diluted PDGFR-a ASODN/lipofectamineTM2000solutionprepared with balanced salt solution in three groups，respectively groupB(1.0μmol/L),C(1.5μmol/L),and D(2.0μmol/L).Another group wasinjected with the equal amount of balanced salt solution recruited as thenormal control group.the left eyes of all animals were not rejected.Slitlamp examination,indirect ophthalmoscopy and electroretinogram(ERG) examination were performed at1,7,14and28days after theinjection.After the last examination,the right eyes were harvested，andHE、immunohistochemistry and transmission electron microscopy ofretinal tissue were performed.Results:The slit lamp,indirect ophthalmoscope examination of allgroups were normal in each time,and pathological changes of the retinaltissue were not observed.ERG examination yielded no difference in theamplitude of b wave between the treated groups and the normal controlgroup.pathological changes of the retinal tissue were not observed in theexaminations of HE and immunohistochemical at28days afte injection.Electron microscope observation of retinal photoreceptor cells in thegroup D: part of gaps between membranous discs were expanding,part ofmembranous discs were fusing,a few of clearances around cell nucleuseswere slightly enlarged,and the shape of the cell nucleus was slightlyirregular. Other pathological changes of retinal cells were not observed infour groups.Conclusions:To inject0.1ml PDGFR-αASODN/lipofectamineTM2000into the vitreous chamber, PDGFR-αASODN can be relatively safe whenits concentration is less than1.5μmol/L.