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May 2017 DOI 10.14302/issn.2470-0436.jos-17-1453
Zhang JieCorresponding author
Department of Ophthalmology, Faculty of Medical and Health Sciences, University of Auckland, Private bag 92019, Auckland 1142, New Zealand.
Purpose: High intraocular pressure (IOP) is known to result in retinal ganglion cell (RGC) loss, both with chronically raised intraocular pressure (such as with glaucoma) and with acute raises in pressure (due to injury or acute angle closure). Because IOP is often raised during ocular surgery, the purpose of this study was to evaluate the effect of transient moderate IOP on retinal function, RGC survival and the expression of Connexin 43 (Cx43) and glial fibrillary acidic protein (GFAP), ubiquitously expressed central nervous system (CNS) proteins that are known to be elevated during the retinal inflammatory response to injury. Materials and Methods: Wistar rats were exposed to transient IOP at 40 mmHg for 5 or 30 minutes, and 60 mmHg for 5 minutes (via cannulation of the anterior chamber with a saline reservoir raised to a height corresponding to the desired IOP), mimicking potential IOP rises during surgery such as DSAEK and some laser procedures (LASIK and femtosecond laser cataract surgery). Separate groups of animals had IOP maintained at 10 mmHg for 5 or 30 minutes as cannulation controls, or 120 mmHg for 60 minutes as positive controls. Changes in the optic nerve and retina were assessed immunohistochemically for GFAP and Cx43 expression. Retinal function was assessed using electroretinography (ERG) recorded at baseline and 14 days after the IOP rise and compared with RGC counts. Results: Results showed that there was a differential GFAP labelling pattern observed in the anterior optic nerve in the 40 mmHg 30 minute and 60 mmHg 5 minute groups 4 hours after manipulation. Gap junction protein Cx43 was minimally up-regulated in the retina in the short-term. There was, however, minimal long-term effect on retinal function and no RGC loss. Conclusions: n conclusion, elevations of IOP that are short in duration such as those occurring during surgical procedures, do not cause significant changes long-term in retinal function or RGC survival. Key Messages: Cx43 and GFAP are known to be elevated during the retinal inflammatory response to injury. No previous study has explored the effect of moderate and relatively short increases in IOP on the initial inflammatory response. We observed a mild glial inflammatory response in the anterior optic nerve, but only a minimal up-regulation of Cx43. However, transient and moderate IOP rises did not induce long term disruption to RGC function or number as measured by electrophysiology and RGC counts, respectively. This is applicable to clinical practice, as it means the IOP elevations that occur during some surgical procedures are unlikely to be causing long term damage in retinal function or RGC survival.
Aug 2016 DOI 10.14302/issn.2474-9273.jbtm-16-1151
Xing GuoqiangCorresponding author
Departments of Anesthesiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814
Oxidative stress mediated neural cell death is thought to be involved in the progression of secondary cell injury following brain trauma. Agents that can block oxidative stress-related injury could be potential therapies for TBI. Resveratrol, a polyphenol found in plants and red wine, is cytoprotective due to its potent antioxidant activities. To further understand how resveratrol could affect oxidative stress-induced injury, we hypothesized that the cytoprotective activities of resveratrol could be dose-dependent. In this study, resveratrol-induced cytoprotection was evaluated in cultured astrocytes. Primary rat astrocytes were cultured in T-75 flasks to a confluence of 80% before being plated onto 96-well plates. After 24 hours of acclimation, astrocytes were treated with various doses of hydrogen peroxide (H2O2) (0.1, 0.25, 0.5 and 1 µM) and resveratrol (25, 50, 75, 100 µM), respectively. Cell viability was determined 24 hours later using Alamar Blue Assay. Treatment of astrocytes with 0.5 mM H2O2, left 65% of astrocytes non-viable whereas treatment of astrocytes with 0.1 mM H2O2 had no effect on astrocytes viability; whereas 1 mM, H2O2 caused total loss of astrocyte viability. Resveratrol treatment at 75 µM and 100 µM has reduced 0.5 mM H2O2-induced cytotoxicity in astrocytes by 50%. Immunostaining with GFAP also confirmed these findings about the cytoprotective effects of resveratrol in astrocytes exposed to H2O2. These results suggest that resveratrol could be a potential neuroprotective agent in TBI due to its antioxidant properties. Further studies are needed to evaluate the long- term effects of resveratrol in animal models of TBI.
Mar 2016 DOI 10.14302/issn.2470-0436.jos-15-739
P. Sarthy VijayCorresponding author
Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, IL 606111.
Ciliary neurotrophic factor (CNTF) is a well-tested, neuroprotective agent that has been shown to retard photoreceptor degeneration in several animal models of retinitis pigmentosa. The molecular mechanisms underlying CNTF-mediated neuroprotection are currently not understood. CNTF could act directly on photoreceptors or it could act indirectly by stimulating Müller glial cells to produce photoreceptor neuroprotective agents. To better characterize CNTF action on Müller cells, we have studied signaling pathways activated by CNTF using an established retinal Müller cell line, rMC-1. RNA was isolated from CNTF-treated cultures, and suppressor of signal transducer and activator of transcription (SOCS3) and Glial fibrillary acidic protein (GFAP) transcript levels were assessed by quantitative real-time PCR. Immunoblotting was used to examine activation ofmitogen activated protein kinase (ERK1/2/MAPK) and phosphoinositide 3-kinase (PI3-K)/Aktpathways in response to CNTF. Additionally, the level of5' AMP-activated protein kinase (AMPK), an enzyme that plays a key role in cellular energy homeostasis levels, was determined by immunoblotting. CNTF treatment resulted strong upregulation of SOCS3 and GFAP transcripts that were blocked by expression of a dominant-negative STAT3 mutant. CNTF treatment also resulted in transient activation of ERK1/2/MAPK but not PI3K/Akt signaling pathway. There was no change in activation of AMPK. We conclude that CNTF treatment leads to stimulation of JAK-STAT and MAPK signaling pathways but not the PI3K/AKT pathway, associated with cell death, in Müller cells.