Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1997-3-11
pubmed:abstractText
In this article, we describe the preliminary results of the development of an animal model that will enable us to study the effect of photoreceptor-derived debris accumulation on the normal function of the retina in vivo. An antisense oligonucleotide (Cat 5), saline, and two control oligonucleotides were injected into the vitreous of 7-week-old RCS-rdy+ rats. The uptake, distribution, and persistence of the antisense oligonucleotide in the retina was demonstrated by fluorescent confocal microscopy, and the stability of the oligonucleotide was shown by GeneScan analysis using a fluorescein-labeled derivative of Cat 5 (Cat 5F). The accumulation of photoreceptor-derived debris was monitored by the number of undigested phagosomes in the RPE layer by light microscopy. Following intravitreal injection of Cat 5F, penetration of the oligonucleotide was observed in the ganglion cell layer in 2 hours and in the photoreceptor and pigment epithelial layers 3 days later. However, at 7, 28, and 56 days postinjection, only the RPE layer had significant amounts of Cat 5F present. Using GeneScan analysis, it was demonstrated that the fluorescein-labeled oligonucleotide present in the RPE layer was not degraded and it retained its original 19-mer length. There was no statistically significant difference in the number of phagosomes found in the RPE layer of control uninjected, saline-injected, and two sense and two antisense oligonucleotides-injected animals at 7 and 28 days postinjection. In contrast, the number of phagosomes was significantly higher (p < 0.001) in the RPE layer of Cat 5 antisense oligonucleotide-injected animals at 7 and 28 days postinjection. This difference, however, disappeared by 56 days postinjection. The inner nuclear layers of the retina of control and experimental animals were not affected by the injections.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1087-2906
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
207-13
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:8915505-Adolescent, pubmed-meshheading:8915505-Analysis of Variance, pubmed-meshheading:8915505-Animals, pubmed-meshheading:8915505-Cathepsins, pubmed-meshheading:8915505-Cells, Cultured, pubmed-meshheading:8915505-Drug Stability, pubmed-meshheading:8915505-Fluorescein, pubmed-meshheading:8915505-Fluoresceins, pubmed-meshheading:8915505-Humans, pubmed-meshheading:8915505-Microinjections, pubmed-meshheading:8915505-Oligonucleotides, pubmed-meshheading:8915505-Oligonucleotides, Antisense, pubmed-meshheading:8915505-Phagosomes, pubmed-meshheading:8915505-Photoreceptor Cells, pubmed-meshheading:8915505-Rats, pubmed-meshheading:8915505-Rats, Inbred Strains, pubmed-meshheading:8915505-Retina, pubmed-meshheading:8915505-Rod Cell Outer Segment, pubmed-meshheading:8915505-Sequence Analysis, DNA
pubmed:year
1996
pubmed:articleTitle
Targeted delivery of an antisense oligonucleotide in the retina: uptake, distribution, stability, and effect.
pubmed:affiliation
Centre for Ophthalmology and Visual Science, University of Western Australia, Nedlands, Australia.
pubmed:publicationType
Journal Article