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Titolo:
Uptake dynamics and retinal tolerance of phosphorothioate oligonucleotide and its direct delivery into the site of choroidal neovascularization through subretinal administration in the rat
Autore:
Shen, WY; Rakoczy, PE;
Indirizzi:
Univ Western Australia, Ctr Ophthalmol & Visual Sci, Perth, WA 6009, Australia Univ Western Australia Perth WA Australia 6009 Perth, WA 6009, Australia
Titolo Testata:
ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT
fascicolo: 4, volume: 11, anno: 2001,
pagine: 257 - 264
SICI:
1087-2906(200108)11:4<257:UDARTO>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
ENDOTHELIAL GROWTH-FACTOR; ANTISENSE OLIGONUCLEOTIDES; MACULAR DEGENERATION; INTRAVITREAL INJECTION; HUMAN CYTOMEGALOVIRUS; EYE; EXPRESSION; THERAPY; RABBIT; PHARMACOKINETICS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Rakoczy, PE Lions Eye Inst, 2 Verdun St, Nedlands, WA 6009, Australia Lions Eye Inst 2 Verdun St Nedlands WA Australia 6009 ustralia
Citazione:
W.Y. Shen e P.E. Rakoczy, "Uptake dynamics and retinal tolerance of phosphorothioate oligonucleotide and its direct delivery into the site of choroidal neovascularization through subretinal administration in the rat", ANTISENSE N, 11(4), 2001, pp. 257-264

Abstract

This study aimed to investigate uptake dynamics and retinal tolerance of phosphorothioate oligonucleotides (PS-oligos) following subretinal injection. A fluorescent-labeled PS-oligo (FL-oligo) with random sequence was administered into the subretinal space of rat by transsclera-choroid-retinal pigment epithelium (RPE) injection at doses of 0.129, 1.29, and 12.9 mug in 2.0mul solution. The uptake dynamics were evaluated by fundus fluorescent photography in real time and by fluorescence microscopy using flat mounts and cryosections. Immunophenotyping for CD4(+), CD8(+) cytotoxic lymphocytes, and CD68(+) macrophages was performed to assess cellular infiltration in theretina. In addition, the FL-oligo was injected subretinally in a rat modelof choroidal neovascularization (CNV) for direct delivery into the site ofCNV. Subretinal administration of FL-oligo resulted in both dose-dependentand time-dependent distribution in the retina, where it accessed the RPE and all layers of the neuroretina. CD4(+), CD8(+) cytotoxic lymphocytes, andCD68+ macrophages were observed at the site of needle penetration. However, in areas far from the injection site where the FL-oligo appeared strongly, cellular infiltration was absent, and the retinal morphology was preserved very well. The FL-oligo was successfully delivered into the site of intense laser photocoagulation. It was predominantly localized to the RPE, macrophages, and some choroid cells and remained detectable for at least 56 daysafter injection. Our results demonstrate for the first time that subretinal injection efficiently introduced PS-oligo into the RPE and neuroretina with an acceptable level of safety. Subretinal administration of antiangiogenic oligonucleotides may hold great potential for the treatment of CNV.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/01/20 alle ore 09:40:10