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Inhibitory Effect Of PTEN On Photoreceptor Cells After Retinal Detachment

Posted on:2016-04-14Degree:DoctorType:Dissertation
Country:ChinaCandidate:D MaoFull Text:PDF
GTID:1104330503993950Subject:Ophthalmology
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Purpose. Apoptosis of photoreceptor cells is the main reason for the poor visual function after retinal detachment. Phosphatase and tensin homology deleted on chromosome 10(PTEN) is crucial in neuronal apoptosis. As a cell survival signaling pathway, the nerve protective effect of PTEN/PI3K/Akt signaling pathway has been confirmed, and its targets are gradually being resolved.This subject adopts the PTEN inhibitor bp V(pic), to study PTEN/PI3K/Akt signaling pathway and its downstream molecules and the change characteristics of the photoreceptor apoptosis, and clarify the regulatory mechanism of PTEN/PI3K/Akt signaling pathway in photoreceptor cell apoptosis caused by retinal detachment(RD).Methods. A rat model of retinal detachment was established, and PTEN expression changes were detected at different time points by Western blotting and immunofluorescence. Some of the rats were given subretinal injections of bp V(pic) after retinal detachment. We documented the expression and distribution of p-Akt and Bcl-2 in the retina by Western blot analysis and immunofluorescence. Levels of p-PDK1, p-BAD, cytosolic cytochrome c(Cyt c) and cleaved Caspase-3 were detected by Western blotting. PIP3 was measured by ELISA. Apoptosis of photoreceptors was detected using the Td T-mediated fluorescein-16-d UTP nick-end labelling(TUNEL) assay. The thickness of the outer nuclear layer(ONL) was also recorded.Results. The expression of PTEN gradually increased after retinal detachment, peaking at 3 d and then decreasing to normal by 7 d after RD. Subretinal injection of bp V(pic) effectively reduced the apoptosis of photoreceptors and preserved the retinal thickness of the ONL after RD. Compared with vehicle-treated RD groups, levels of p-Akt and p-PDK1 were significantly upregulated in bp V-treated RD groups. In addition, bp V treatment increased the levels of p-BAD and Bcl-2 and decreased the expression levels of cytosolic Cyt c and cleaved caspase-3 after RD.Conclusions. PTEN participates in the apoptosis of photoreceptors after retinal detachment. Blocking PTEN may reactivate the PI3K/Akt pathway and attenuate photoreceptor apoptosis by suppressing the mitochondrial pathway.
Keywords/Search Tags:PTEN, retinal detachment, photoreceptor, apoptosis, PI3K/Akt signalling pathway
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