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W. Cao, R.V. Rajala, F. Li, R.E. Anderson, M. Dittmar, C.E. Soliman, S. Li, Y. Zhu, J.F. McGinnis; In vivo Protection of Photoreceptors from Light Damage in Rat by 17 ß-estradiol . Invest. Ophthalmol. Vis. Sci. 2003;44(13):5123.
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Purpose: To examine whether 17 ß-estradiol (ßE2) exhibits neuroprotective activity in vivo for photoreceptor cells. Methods: Sprague-Dawley albino rats raised in 5 lux cyclic light (12 hr ON:12hr OFF) were injected intraperitoneally (IP) with ßE2 (1 mg/kg body weight in 1% ethanol) or 1% ethanol as vehicle. Animals were exposed to constant light for 24 hrs at an illuminance level of 1700 lux. The electroretinogram was recorded to evaluate functional protection and the morphologic protection was evaluated by quantitative histology. The apoptotic cell death of photoreceptor cells was also evaluated by the TdT-mediated digoxigenin-dUTP nick-end labeling (TUNEL) assay. Western blot analysis was performed to determine the levels of the p85 regulatory subunit of phosphoinositide 3-kinase (PI3K), Akt, phosphorylated Akt (pAkt), insulin receptor ß–subunit (IRß), and insulin-like growth factor-1 receptor (IGF-1R). The PI3K activity was also measured using PI-4,5-P2 as substrate. GST pull-down assays were performed employing GST-p85 NSH2 domain to measure the activation of IRß. Results: IP injection of ßE2 significantly protected photoreceptors against light damage, as demonstrated by TUNEL assay and by quantitative function and morphologic measurements. Both IRß and IGF-IR are present in the rat retina. However, ßE2 activated specifically IRß but not IGF-IR. IP injection of ßE2 was found to significantly increase PI3K activity as well as pAkt levels in a time-dependent manner. Conclusions: 17 ß-estradiol can attenuate light-induced photoreceptor degeneration in vivo. The insulin/PI3K/Akt signal pathway may be involved in the neuroprotective effect of ßE2 through a mechanism that remains to be elucidated.
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