Protective effects of resveratrol in experimental retinal detachment. Huang Wei,Li Guorong,Qiu Jianming,Gonzalez Pedro,Challa Pratap PloS one BACKGROUND:Oxidative stress is one of the major factors that trigger photoreceptor apoptosis. To investigate whether resveratrol, a potent antioxidant and small molecule activator of the FoxO pathway, would be neuroprotective against photoreceptor cell death in a rodent model of retinal detachment. METHODS:Retinal detachment was created in adult Brown Norway rats by subretinal injection of sodium hyaluronate. The animals were treated daily with vehicle or resveratrol (20 mg/kg) intraperitoneal injection. Photoreceptor death was assessed by counting the number of apoptotic cells with TdT-dUTP terminal nick-end labeling (TUNEL) and measurement of the outer nuclear layer (ONL) thickness 3 days after RD. Changes in expression of FoxO1a, FoxO3a, and FoxO4 were analyzed by western blot. The activity of caspase 3, caspase 8, caspase 9, spectrin and their cleavage forms were studied. RESULTS:Three days after retinal detachment, caspase 3, caspase 8 and caspase 9 were significantly activated in the detached retina. Spectrin cleavage products at 120 and 145 kDa were also detected. Both caspase and calpain activation are involved in apoptotic photoreceptor cell death in detached retinas. Treatment with resveratrol increases FoxO1a, FoxO3a, and FoxO4 protein expression in detached retinas only. Resveratrol treatment decreases activation of intrinsic and extrinsic caspase apoptotic pathways triggered by RD. The number of TUNEL-positive cells decreases from 1301±51 cells/mm(2) in control groups to 430±35 cells/mm(2) in treatment groups (p<0.05). Resveratrol treatment also demonstrates 59% less ONL thickness loss compared to controls. CONCLUSIONS:Resveratrol treatment up-regulates the FoxO family and blocks Caspase3, 8, and 9 activation. Resveratrol has the potential to be used as a novel therapeutic agent for preventing vision loss in diseases characterized by photoreceptor detachment. 10.1371/journal.pone.0075735

Role of AMPK-regulated autophagy in retinal pigment epithelial cell homeostasis: A review. Medicine The retinal pigment epithelium (RPE) is a regularly arranged monolayer of cells in the outermost layer of the retina. It is crucial for transporting nutrients and metabolic substances in the retina and maintaining the retinal barrier. RPE dysfunction causes diseases related to vision loss. Thus, understanding the mechanisms involved in normal RPE function is vital. Adenosine monophosphate-activated protein kinase (AMPK) is an RPE energy sensor regulating various signaling and metabolic pathways to maintain cellular energetic homeostasis. AMPK activation is involved in multiple signaling pathways regulated by autophagy in the RPE, thereby protecting the cells from oxidative stress and slowing RPE degeneration. In this review, we attempt to broaden the understanding of the pathogenesis of RPE dysfunction by focusing on the role and mechanism of AMPK regulation of autophagy in the RPE. The correlation between RPE cellular homeostasis and role of AMPK was determined by analyzing the structure and mechanism of AMPK and its signaling pathway in autophagy. The protective effect of AMPK-regulated autophagy on the RPE for gaining insights into the regulatory pathways of RPE dysfunction has been discussed. 10.1097/MD.0000000000038908

Integrated bioinformatic changes and analysis of retina with time in diabetic rats. Cui Zekai,Zeng Qiaolang,Guo Yonglong,Liu Shiwei,Chen Jiansu PeerJ Diabetic retinopathy (DR) is the most common chronic complication of diabetes. It can cause impaired vision and even blindness. However, the pathological mechanism of DR is still unknown. In the present study, we use bioinformatic analysis to reveal the pathological changes of early DR in a streptozotocin (STZ) induced diabetes rat model. The dataset GSE28831 was downloaded from the Gene Expression Omnibus (GEO) database. To clarify the pathological mechanism of early DR, genes which were up-regulated (UP group) or down-regulated (DOWN group) over time were identified. One hundred eighty six genes in the UP group and 85 genes in the DOWN group were defined. There were in total 28 Gene ontology (GO) terms with a value lower than 0.05 in UP group, including astrocyte development, neutrophil chemotaxis, neutrophil aggregation, mesenchymal cell proliferation and so on. In the DOWN group, there were totally 14 GO terms with a value lower than 0.05, including visual perception, lens development in camera-type eye, camera-type eye development, bicellular tight junction and so on. Signaling pathways were analyzed with all genes in the UP and DOWN groups, and leukocyte transendothelial migration and tight junction were selected. Protein-protein interaction (PPI) network was constructed and six hub genes , , , , and were selected with connection degree ≥5. , and may be potential targets for DR diagnosis and treatment. This study provides the basis for the diagnosis and treatment of DR in the future. 10.7717/peerj.4762