17β-Estradiol Protects the Retinal Nerve Cells Suppressing TLR2 Mediated Immune-Inflammation and Apoptosis from Oxidative Stress Insult Independent of PI3K.

The excessive apoptosis of retinal nerve cells (RNCs) could cause a variety of retinal neurodegenerative diseases which could result in the irreversible blindness. In this study, the experiment models of H2O2 and light-induced oxidative insult in the retina of Sprague-Dawley (SD) rat were used. We demonstrated the role of toll-like receptor 2 (TLR2) in apoptosis and immune-inflammation induced by oxidative stress insult. Meanwhile, we also tried to elucidate the modulating mechanism of 17β-estradiol (E2) resistant to TLR2 induced by oxidative stress insult. The cell apoptosis induced by oxidative stress was examined by annexin V-FITC/propidium iodide (PI) assay using flow cytometry and the expressions of TLR2 and inflammatory cytokines were determined by real-time PCR and western blotting. Peptidoglycan (PGN) as the ligand of TLR2 and small interfering RNAs of TLR2 (siTLR2) were used to determine the role of TLR2. From the results, firstly, we demonstrated that E2 could reduce the expressions of TLR2 and inflammatory cytokines including TNF-ɑ, IFN-γ, and IL-1β induced by oxidative stress; secondly, the phosphoinositide 3-kinase (PI3K) could not influence the effect of E2 on reducing TLR2 expression induced by H2O2 in RNCs; thirdly, PGN could promote the damage effect of H2O2 by transforming RNCs from late apoptosis to necrosis, however, E2 could decrease the cell apoptosis mediated by PGN; and finally, the apoptosis of RNCs and the expressions of the inflammatory cytokines induced by H2O2 administration were significantly inhibited after TLR2 interference. In summary, E2 reduces the TLR2-mediated immune-inflammation, thereby protecting RNCs against oxidative stress-induced apoptosis via a PI3K-independent signaling pathway. The present results provide evidence that inhibiting of TLR2-mediated immune-inflammation might be a possible therapeutic way to exert auxiliary role on E2 neuroprotection.