Two are better than one: Unraveling the functions of cone arrestin in zebrafish (Commentary on Renninger, Gesemann and Neuhauss)

Since the surprising discovery of a second visual arrestin in mammalian pinealocytes and cone photoreceptors, numerous studies have examined cone arrestin's structural and functional similarities to and differences from rod arrestin (Craft et al., 1994; Nikonov et al., 2008). The rod arrestin or Arrestin1 binds to and terminates the light-activated, phosphorylated G-protein-coupled rhodopsin (Xu et al., 1997), whereas both visual arrestins work in concert in cone photoreceptors to shut off the light-activated photoreceptor signal transduction cascade, as shown for mouse Sand M-opsin (Nikonov et al., 2008). In this issue of EJN, Renninger and colleagues add a new dimension to understanding the visual arrestin saga by introducing two rod arrestins (arrS), three b-arrestins, and focusing on two paralogs of cone arrestin (arr3a and arr3b) in the zebrafish (Danio rerio). The Arr3a is exclusively expressed in M- and L-wavelength sensitive cones, whereas Arr3b is found in S- and UV-wavelength-sensitive cones. Their comprehensive study provides the first clear evidence of Arr3a's involvement in the high temporal contrast sensitivity of cone vision. As zebrafish exhibit light responses after 3 days of development, they are an ideal animal to study visual behavior (Brockerhoff et al., 1995). They are tetrachromatic with ultraviolet-sensitive cones as well as red-, green- and blue-sensitive cones, and their retinas continue to grow throughout their life. Using this cone-dominated visual system as a model system for their analysis, Renninger et al. (2011) examined the cellular expression of the distinct isoforms of arrestin in the visual system using a combination of in-situ hybridization and cone arrestin paralog-specific antibodies to examine cellular distribution at different developmental stages. These straightforward morphological experiments were followed by a set of elegant physiological experiments using targeted gene knockdown of the two cone arrestins in zebrafish larvae to unravel their visual responses with electroretinography. The functional knockdown of arr3a led to an electroretinography photo-response recovery delay. Additional experiments with the functional inactivation of arr3a were used to dissect out the psychophysical responses with optokinetics, a stereotypic ocular movement that is probably mediated by the modulation of M- and L-cone input (Orger & Baier, 2005). These latter experiments distinguished behavioral differences between low-contrast (dark-adapted) conditions that affected high temporal frequency patterns, and high-contrast (lightadapted) conditions that showed a deceleration of the temporal transfer function in the arr3a morphant larvae. Because of the lower abundance of the S- and UV-wavelength-sensitive cones in zebrafish, the function of arr3b remains undetermined; however, this work provides conclusive evidence that arr3a regulates high temporal resolution in high acuity color vision with experiments that are not possible in the rod-dominant mammalian retina. This work illustrates the use of the zebrafish as a vertebrate model to address the basic cellular function of cone arrestin and contributes to our broader understanding of visual processing and the complex physiology of high acuity color vision

Cyclic Ovarian Hormone Modulation of Supraspinal Δ\u3csup\u3e9\u3c/sup\u3e-tetrahydrocannabinol-induced Antinociception and Cannabinoid Receptor Binding in the Female Rat

Estrous cycle-related fluctuations in delta-9-tetrahydrocannabinol (THC)-induced antinociception have been observed in the rat. The aim of this study was to determine which major ovarian hormone modulates the antinociceptive effects of i.c.v. THC, and whether hormone modulation of THC\u27s behavioral effects could be due to changes in brain cannabinoid receptors (CBr). Vehicle (oil) or hormones (estradiol or progesterone, or both) were administered to female rats on days 3 and 7 post-ovariectomy. On the morning or afternoon of day 8 or day 9, vehicle or THC (100 μg) was administered i.c.v. Paw pressure, tail withdrawal, locomotor activity and catalepsy tests were conducted over a 3-h period. Estradiol (with and without progesterone) enhanced THC-induced paw pressure antinociception only. Ovarian hormones time-dependently modulated CBr in brain structures that mediate antinociception and locomotor activity, but the changes observed in CBr did not parallel changes in behavior. However, the time course of CBr changes must be further elucidated to determine the functional relationship between receptor changes and antinociceptive sensitivity to THC

E Pluribum Una Ecclesia: Addressing Ideologically Driven Disunity Through a Multifaceted Approach

Pastors and church leaders within the Rocky Mountain Church Network, an association of 48 churches, face difficulty caused by ideologically driven disunity (IDD). Current polling shows IDD\u27s negative effect on pastors, church leaders, and congregations. Due to the foundational nature of ideologies, attempts to alleviate IDD have typically worsened the situation. This action research project seeks to identify the presence and impact of IDD as well as provide a strategy and tools to address IDD in a congregation. Using surveys, focus groups, and personal interviews, the researcher acquired quantitative and qualitative data from 22 project participants that affirmed the data revealed and discussed in the current literature. The researcher created three primary tools for addressing IDD: a three-week devotional detailing the relationship between the Great Commission and congregational unity, a three-week sermon series, and a presentation that gave research results, conclusions from the data, and the strategy for addressing IDD. As ideologically driven disunity is present in many churches and other scenarios, this research project has the potential to assist leaders in various settings address IDD. By understanding the nature of ideologies, possessing tools to address IDD, and focusing on the mission of the organization, organizational leaders in churches inside and outside the Rocky Mountain Church Network, as well as in secular settings, can help the groups they lead to be more effective and minimize stress in their own lives

Retinal Neovascular Disorders: Mouse Models for Drug Development Studies

Neovascularization is a hallmark of several eye diseases leading to visual impairment, and its epidemiological impact is substantial (Lee et al. 1998). In retinal degenerative disease models, neovascularization is the process by which the choroid and/or retina become infiltrated with new blood vessels. In retinal neovascularization (RNV), sprouting retinal vessels penetrate the inner limiting membrane (ILM) and grow into the vitreous, and in some cases, grow through the avascular outer retina into the subretinal space (Campochiaro 2000). Numerous clinical and ­experimental observations indicate that ischemia (or hypoxia) is the driving force behind RNV (Michaelson and Steedman 1949). Occlusion of retinal vessels leading to ischemia is a feature of diseases with RNV, including diabetic retinopathy (DR) and retinopathy of prematurity (ROP) (Campochiaro 2000)