Redox-regulated growth factor survival signaling.

Significance: Once the thought of as unwanted byproducts of cellular respiration in eukaryotes, reactive oxygen species (ROS) have been shown to facilitate essential physiological roles. It is now understood that ROS are critical mediators of intracellular signaling. Control of signal transduction downstream of growth factor receptors by ROS is a complex process whose details are only recently coming to light.

Reactive oxygen species regulate prosurvival ERK1/2 signaling and bFGF expression in gliosis within the retina.

Purpose: Gliosis is the response of glial cells within retinal tissue to injury. It can be beneficial in the short term, but if the response is extended it can lead to scar formation, which contributes to blindness. Phosphorylation of extracellular signal regulated kinase 1/2 (ERK1/2) is considered to be a hallmark event of gliosis, but the factors involved throughout its associated signaling pathway remain poorly understood, particularly in the retina.

Preventing retinal apoptosis--is there a common therapeutic theme?

There is an urgent need for therapies for retinal diseases; retinitis pigmentosa sufferers have no treatment options available and those targeted at other retinopathies have shown limited effectiveness. The process of programmed cell death or apoptosis although complex, remains a possible target for the treatment of retinal diseases. Having identified apoptosis in the vertebrate retina in populations of immature neurons as an essential part of development it was proposed that re-activation of these developmental cell death pathways might provide insight into the death mechanisms operating in retinal diseases.

Monopolar vs. bipolar subretinal stimulation-an in vitro study.

This study uses an in vitro rd10 mouse model to quantify and compare the ability of the monopolar and the (concentric) bipolar electrode configurations for subretinal stimulation. To allow for results which can be directly compared an identical region of the retina was stimulated due to the circumstance that the bipolar electrode configuration allows also for monopolar stimulation, if the concentric counter-electrode is set potential-free (floating). A ganglion cell, located centrally over the bipolar electrode configuration was selected to extracellularly record action potentials during stimulation.

Rod and cone photoreceptor cells produce ROS in response to stress in a live retinal explant system.

Purpose: The production of reactive oxygen species (ROS) can lead to oxidative stress, which is a strong contributory factor to many ocular diseases. In this study, the removal of trophic factors is used as a model system to investigate the effects of stress in the retina. The aims were to determine if both rod and cone photoreceptor cells produce ROS when they are deprived of trophic factor support and to demonstrate if the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) enzymes are responsible for this ROS production.

Hydrogen peroxide as a cell-survival signaling molecule.

Reactive oxygen species (ROS) were seen as destructive molecules, but recently, they have been shown also to act as second messengers in varying intracellular signaling pathways. This review concentrates on hydrogen peroxide (H2O2), as it is a more stable ROS, and delineates its role as a survival molecule. In the first part, the production of H2O2 through the NADPH oxidase (Nox) family is investigated.

Stress-induced activation of Nox contributes to cell survival signalling via production of hydrogen peroxide.

Reactive oxygen species (ROS) have traditionally been viewed as a toxic group of molecules; however, recent publications have shown that these molecules, including H(2)O(2), can also strongly promote cell survival. Even though the retina has a large capacity to produce ROS, little is known about its non-mitochondrial sources of these molecules, in particular the expression and function of NADPH oxidase (Nox) proteins which are involved in the direct generation of superoxide and indirectly H(2)O(2). This study demonstrated that 661W cells, a retina-derived cell line, and mouse retinal explants express Nox2, Nox4 and certain of their well-established regulators.

Co-operative Cdc42 and Rho signalling mediates ephrinB-triggered endothelial cell retraction.

Cell repulsion responses to Eph receptor activation are linked to rapid actin cytoskeletal reorganizations, which in turn are partially mediated by Rho-ROCK (Rho kinase) signalling, driving actomyosin contractility. In the present study, we show that Rho alone is not sufficient for this repulsion response. Rather, Cdc42 (cell division cycle 42) and its effector MRCK (myotonic dystrophy kinase-related Cdc42-binding kinase) are also critical for ephrinB-induced cell retraction.