PI3K/AKT AND NF-kB ACTIVATION FOLLOWING INTRAVITREAL ADMINISTRATION OF 17p-ESTRADIOL: NEUROPROTECTION OF THE RAT RETINA FROM LIGHT-INDUCED APOPTOSIS

摘要

Abstract-The neuroprotective role of 17p-estradiol is well known; however, its mechanism of action remains unclear. In the present study, we applied light-induced apoptosis on the Sprague-Dawley rat retina to determine the neuroprotective effect of intravitreal administration of 17p-estradiol on retinal neurons and to demonstrate its underlying mechanism of action. Fourteen days after ovariectomy, adult female Sprague-Dawley rats received light damage. The functional and morphological changes of the retina were monitored by electroretinogram and hematoxylin and eosin staining, respectively. Retinal apoptosis was characterized by the presence of DNA laddering and positive terminal deoxyuri-dine triphosphate (dUTP) nick-end labeling. The phosphoin-ositide 3-kinase (PI3K)-specific inhibitor LY294002 was used to elucidate whether the PI3K/Akt signaling pathway was activated by 17p-estradiol. Western blotting was used to detect the activation of caspase 3 and Akt. Immunofluorescence was performed to determine the translocation of NF-kB. Our data showed that exposure to 8000 lux white light for 12 h resulted in functional damage to the rat retina, histological changes and retinal neuronal apoptosis. 17p-Estra-diol significantly rescued retinal function by preventing neuronal apoptosis. Moreover, the inhibition of Akt activation by LY294002 increased retinal neuronal apoptosis, demonstrating that the PI3K/Akt signaling pathway is involved. Levels of cleaved caspase-3 were suppressed in the presence of 17p-estradiol, while LY294002 reversed the effects. It is noteworthy that NF-kB p65 also translocated from the cytoplasm to the nucleus after 17p-estradiol administration.