PMC:4277126 / 55577-59729 JSON TXT

Annnotations TAB JSON ListView MergeView

2_test

{"project":"2_test","denotations":[{"id":"25552899-24400114-26094279","span":{"begin":377,"end":379},"obj":"24400114"},{"id":"25552899-23094016-26094280","span":{"begin":380,"end":382},"obj":"23094016"},{"id":"25552899-23094016-26094281","span":{"begin":391,"end":393},"obj":"23094016"},{"id":"25552899-23094016-26094282","span":{"begin":1310,"end":1312},"obj":"23094016"},{"id":"25552899-24400114-26094283","span":{"begin":1787,"end":1789},"obj":"24400114"},{"id":"25552899-24400114-26094284","span":{"begin":3186,"end":3188},"obj":"24400114"},{"id":"25552899-24400114-26094285","span":{"begin":3766,"end":3768},"obj":"24400114"},{"id":"25552899-24400114-26094286","span":{"begin":4011,"end":4013},"obj":"24400114"}],"text":"Experimental glaucoma: acute ocular hypertension\nAcute ocular hypertension (AOH) is a well-established animal model for producing retinal degeneration, which has been used to investigate the pathogenesis of RGC death and possible therapeutic interventions for neuroprotection. Several animal studies have shown the protective effects of LBPs against AOH-induced retinal injury.78,79\nMi et al79 evaluated the protective effect of LBPs on retinal I/R injury in male C57BL/6N mice. The mice were treated in unilateral eye for 1 hour by introducing 90 mmHg ocular pressure to induce AOH. The animals were administered with 1 mg/kg LBPs daily from 7 days before the I/R insult till sacrifice at either day 4 or day 7 post-insult. The neuroprotective effects of LBPs on RGCs and BRB were assessed. In control AOH retina, loss of RGCs, thinning of inner retinal layer thickness, increased immunoglobulin G (IgG) leakage, broken tight junctions, and decreased density of retinal blood vessels were observed. However, in LBP-treated AOH retina, there was less loss of RGCs with thinning of inner retinal layer thickness, IgG leakage, more continued structure of tight junctions associated with higher level of occludin protein, and the recovery of the blood vessel density when compared with vehicle-treated AOH retina.79 Moreover, LBPs provide neuroprotection by downregulating advanced glycation end products and their receptors, endothelin-1, and amyloid-β (Aβ) in the retina, as well as their related signaling pathways, which was related to inhibiting vascular damages and the neuronal degeneration in AOH insults. These data suggest that LBPs could prevent damage to RGCs from AOH-induced ischemic injury and that LBPs may be a potential treatment for vascular-related retinopathy.\nHe et al78 further explored the mechanisms for LBP-mediated protective effects on AOH-induced retinal injury in eight-week-old male Sprague–Dawley rats. The left eye of rats was subject to increased intraocular pressure of 130 mmHg for 60 minutes using a physiological saline reservoir to induce AOH. Successful achievement of retinal ischemia was confirmed by the collapse of the central retinal artery and the whitening of the iris during the elevation of intraocular pressure. About 1 mg/kg/day LBPs was administered by gavage for 7 days before AOH procedure. The protective effects of LBPs were evaluated by quantifying ganglion cell and amacrine cell survival and by measuring cellular apoptosis in the retinal layers. In addition, the expression of heme oxygenase-1 (HO-1) was examined using Western blotting and immunofluorescence analyses. The redox-sensitive transcription nuclear factor erythroid 2-related factor (Nrf2) in cytosol and nucleus was measured using immunofluorescent staining. HO-1 is the rate-limiting enzyme that catalyzes the degradation of heme into biliverdin, carbon monoxide, and iron, and is one of the phase II detoxifying enzymes and antioxidants that are closely regulated by Nrf2. Increased apoptosis and decreased number of viable cells were observed in the ganglion cell layer (GCL) and inner nuclear layer (INL) in the I/R retina, which were reversed by LBP treatment.78 In LBP-pretreated rats, the rate of RGC loss was delayed and more than 50% of RGCs remained viable in the retina 7 days after the ischemic insult. When compared with the vehicle-treated I/R retina, the LBP-treated I/R retina had an increase in the number of choline acetyltransferase-positive retinal amacrine cells. The retinal level of radical oxygen species (ROS) was decreased by LBP pretreatment in I/R mice. Similar to the specific Nrf2 activator, sulforaphane, LBP pretreatment significantly increased the number of RGCs with nuclear translocation of Nrf2 in I/R retina.78 Retinal HO-1 expression determined by immunofluorescent staining and immunoblotting was also upregulated by LBPs. Inhibition of HO-1 activity by zinc protoporphyrin at 20 mg/kg abolished LBP-induced protective effects in the retina after I/R.78 The data demonstrate that LBPs elicit retino- and neuro-protective effects via the activation of Nrf2 and upregulation of HO-1 expression."}

NEUROSES

PMC:4277126 / 55577-59729 JSONTXT

Annnotations TAB JSON ListView MergeView

2_test

NEUROSES

PMC:4277126 / 55577-59729 JSON TXT