Middle cerebral artery occlusion-induced ischemic retinal injury
Li et al77 investigated the effects of intragastric LBP pretreatment by gavage on the retinal injuries induced by middle cerebral artery occlusion (MCAO) in C57BL/6N male mice. Prior to induction of MCAO, mice were treated orally with 1 mg/kg LBPs once a day for 1 week. Retinal ischemia was maintained for 2 hours, after which the filament was pulled out to allow reperfusion for 22 hours. Viable cells in GCL of the central and peripheral retina were counted and retinal swelling was evaluated by measuring the inner retinal thickness from the inner limiting membrane to INL. Expression levels of glial fibrillary acidic protein (GFAP), aquaporin-4 (AQP4), poly(ADP-ribose) (PAR), and nitrotyrosine (NT) in mouse retina were determined by immunohistochemistry. The integrity of BRB was assessed by measuring IgG extravasation. The study showed that the number of viable cells in GCL in the central and the peripheral retina was significantly higher in the LBP-treated I/R mice compared with that in the vehicle-treated I/R mice.77 There was a decrease in inner retinal thickness of the central retina in the LBP-treated I/R mice when compared with the vehicle-treated I/R mice. Fewer apoptotic cells were found in GCL and INL of the LBP-treated I/R retina when compared with that of the vehicle-treated I/R retina. Protein kinase C-alpha expression (a marker for rod bipolar cells) in the LBP-treated I/R retina was more when compared with that in the vehicle-treated I/R retina.77 The expression of calretinin by amacrine cells was higher in LBP-treated I/R retina compared with that of the vehicle-treated I/R retina. There were more neuronal NO synthase-expressing amacrine cells found in the LBP-treated I/R retina compared with the vehicle-treated I/R retina. Disruption of BRB leads to swelling of astrocytes and Muller cells processes associated with the activation of GFAP and AQP4 under ischemic conditions. The immunoreactivity of GFAP in astrocytes in GCL was reduced in LBP-treated I/R retina compared with that of the vehicle-treated I/R retina. The immunoreactivity of AQP4 expressed in the astrocytes of inner limiting membrane and INL was significantly lower in LBP-treated I/R retina compared with the vehicle-treated I/R retina. LBP treatment also reduced the number of retinal blood vessels with IgG leakage, nuclear translocation of PAR expression, and NT expression.77 The breakdown of DNA strands activates the nuclear enzyme poly(ADP-ribose) polymerase (PARP) to produce PAR. Free radical formation facilitates NO production, which reacts with superoxide to from peroxynitrite, a strong oxidant that leads to nitration of tyrosine residues of cells to form NT. These results show that pretreatment of mice with LBPs effectively protected the retina from RGC apoptosis, retinal swelling, glial cell activation, BRB disruption, and oxidative stress.