Reactivation of the PI3K/Akt Signaling Pathway by the Bisperoxovanadium Compound bpV(pic) Attenuates Photoreceptor Apoptosis in Experimental Retinal Detachment.
OBJECTIVE
Phosphatase and tensin homology deleted on chromosome 10 (PTEN) is crucial in neuronal apoptosis. This study evaluated the role of PTEN in photoreceptor cell apoptosis caused by retinal detachment (RD).


METHODS
A rat model of RD 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 bisperoxovanadium compound (bpV[pic]) after RD. We documented the expression and distribution of phospho-Akt (p-Akt) and B-cell lymphoma 2 (Bcl-2) in the retina by Western blot analysis and immunofluorescence. Levels of phosph-phosphoinositide-dependent kinase 1 (p-PDK1), phospho-Bcl-2 death promotor (p-BAD), cytosolic cytochrome c (Cyt c), and cleaved Caspase-3 were detected by Western blotting. We measured phosphatidylinositol 3,4,5-triphosphate (PIP3) by ELISA. Apoptosis of photoreceptors was detected using the TUNEL assay. The thickness of the outer nuclear layer (ONL) also was recorded.


RESULTS
The expression of PTEN gradually increased after RD, peaking at 3 days and then decreasing to normal by 7 days after RD. Subretinal injection of bpV(pic) effectively reduced the apoptosis of photoreceptors and preserved the retinal thickness of the ONL after RD. Compared to vehicle-treated RD groups, levels of p-Akt and p-PDK1 were significantly upregulated in bpV-treated RD groups. In addition, bpV 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
Phosphatase and tensin homology deleted on chromosome 10 (PTEN) participates in the apoptosis of photoreceptors after RD. Blocking PTEN may reactivate the PI3K/Akt pathway and attenuate photoreceptor apoptosis by suppressing the mitochondrial pathway.
Dan
D
Mao
Xiaodong
X
Sun
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism*; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D012160:Retina / Q000378:metabolism; D012163:Retinal Detachment / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D015398:Signal Transduction; D014639:Vanadium; D017968:Vanadium Compounds / Q000494:pharmacology*
D017968:Vanadium Compounds; C472777:bisperoxovanadium; D014639:Vanadium; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt