Signal Transduction in the Retina PDF

Preface

In the current "postgenomic era," there is increasing recognition of the need for integrated approaches to study and understand complex biological systems and signaling networks. The retina—an anatomically and functionally unique part of the central nervous system, responsible for the detection and initial processing of visual information—is illustrative of this. An integrated knowledge of the biochemistry, cell biology, physiology, and physics of phototransduction, as well as postphotoreceptor visual transduction processes, has evolved over the past century, with the finer details becoming apparent particularly within the past decade. The retina is an extremely useful biological system amenable to experimental manipulation in vivo as well as in vitro, affording an accessible model with which to understand individual cellular signaling systems down to the level of molecular interactions at atomic resolution, as well as more complex issues of pathway regulation and the integration of signaling networks that impact cellular and tissue responses, ultimately resulting in visual perception

The present volume, comprised of fifteen chapters in six sections, brings together a number of internationally recognized authorities in disciplines pertinent to the study of signal transduction in the retina. Each chapter presents a brief overview of the background and current state of knowledge in a particular area relevant to the broader topic of retinal signal transduction, along with detailed information regarding specific methodology for obtaining the primary data necessary to understand the molecular and cellular processes being examined. Because more is known about the rhodopsin-based phototransduction pathway in vertebrate retinal rod cells than in almost any other biological system, and this dominates signaling processes in the retina, a substantial portion of this volume is devoted to that topic. In addition, a diversity of other signaling mechanisms and systems are covered, affording the reader a resource for evaluating the similarities and differences between these systems and the specific research strategies employed for studying them.

Section 1 deals with the molecular mechanisms of vertebrate phototransduction, dissecting the major components of the phototransduction cascade in rod cells and proteins involved in its regulation. The chapters in this section emphasize the breadth of knowledge accumulated in the past decade, especially with regard to determination of the molecular structure of phototransduction cascade components at atomic resolution, as well as the use of transgenic strategies. State-of-the-art approaches for the study of molecular interactions in multiprotein complexes, as well as novel cellbased strategies aimed at understanding the mechanisms of signal shut-off and light adaptation, are presented.

Section 2 focuses on the more recently emerging field of nonvisual phototransduction. Methods for assessing the roles of melanopsin in regulation of the circadian clock and in adaptive photoresponses are described.

Section 3 provides a chapter devoted to essential methods for studying phototransduction in the invertebrate retina, using Drosophila as the biological system of choice. Thus, the reader will be able to compare and contrast the juxtaposing processes of visual signaling in vertebrates versus invertebrates.

Section 4 focuses on experimental studies of insulin-based signaling in the retina, both in the outer retina (photoreceptors, per se) as well as inner retinal cells. In addition, insulin receptor structure and ligand-binding specificity as well as mechanisms of downstream signaling are described.

Section 5 presents current methodological approaches relevant to retinal development, including cellular signaling in retinal progenitor cells, and cell–cell communications in developing retina. Because neovascularization is considered an increasingly important factor in various human degenerative retina diseases, particularly those that accompany diabetes and aging, this section also addresses experimental approaches for studying vascular homeostasis.

Section 6 deals with recent developments in the field of lipid-derived mediators, particularly neuroprotectins and the participation of the retinal pigment epithelium in neuronal survival in the retina.

Now in the twenty-first century, we are just beginning to understand the enormous diversity and complexity of signaling processes in the retina. The methodologies and experimental approaches described in this volume have already yielded key fundamental information regarding the cellular and molecular mechanisms that underlie normal retinal physiology. In addition, they have the potential to provide new clues toward elucidating the mechanisms involved in retinal disease processes as well as the development of novel therapeutic approaches for preventing, arresting, and modulating those disease processes and promoting cellular survival and retention of function.