Alexa Karina Klettner - Retinal Pigment Epithelium in Health and Disease

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When studying the eye, one cannot help to be fascinated by its complexity, its functionality, and its beauty. When working on the retina, the most fascinated cell, at least in our humble opinion, is the retinal pigment epithelium (though we do acknowledge that opinions might differ here, researchers tend to find their own field to be the most interesting subject in the world). The retinal pigment epithelium (RPE) has many functions, many aspects, and many ways to be elucidated. When this introduction was written, the term retinal pigment epithelium had 14,142 hits in PubMed. We are aware that neither we nor any other book could possibly do justice to the knowledge about this cell type, nor do we make any claim to be complete. However, the last comprehensive book on the retinal pigment epithelium was published more than 20 years ago, and we felt the urge and the need to present a compendium on the modern RPE, as it is studied in the twenty-first century.

We have divided the book in five different aspects: (1) physiological RPE function, (2) RPE in disease, (3) RPE in diagnostics, (4) RPE in therapy, and (5) RPE models to portray the different aspects of RPE research.

In the first chapter, RPE Histopathology and Morphometry,Szalai,Nickerson, andGrossniklausintroduce the histology, morphology, distribution, and topography of these cells, comparing the physiological appearance with changes seen in age and furthermore in pathological conditions such as age-related macular degeneration, retinal dystrophies, proliferative retinopathies, mitochondrial disease, and tumors.

A major characteristic of the RPE is its polarity, and the functions associated with it.Rizzologives an overview on RPE Polarity and Barrier Function, describing the unique polarity of the RPE (considered to be upside down or rather right side up due to reversed membrane polarity), explaining the blood-retinal-barrier and its maturation and the structure and composition of tight junctions, stressing the claudins, and introducing reader into the ways of analyzing barrier function. Finally, the breakdown of the barrier in pathological situation, such as edema, is covered.

A major function of the polarized RPE cells is the phagocytosis of shed photoreceptor outer segment fragments, which is covered in this volume byMller and Finnemannin their chapter RPE Phagocytosis. The authors introduce the reader to the experimental approaches to study phagocytosis in RPE cells and give insights into the molecular mechanisms of phagocytosis, including the recognition and binding by the RPE cells, consequent signaling pathways, as well as processing and degradation of the phagocytosed material. Finally, they cover defects in the process and its relevance to retinal diseases.

In order to fulfill its functions, ion channels play an important part in RPE cells. In their chapter Ion Channels of the Retinal Pigment Epithelium,ReichhartandStraussintroduce the reader into the profile, function, and pathological role of ion channels. Both apical and epithelial transports are covered, as well as their role of ion buffering in the subretinal space. Also, a major topic is the role of Ca2+signaling in RPE function.

Vascular endothelial growth factor (VEGF) is a major cytokine in health and disease in the retina, with the RPE being an important source, as described in this volume byKlettner. The chapter RPE and the Vascular Endothelial Growth Factor introduces VEGF and its regulatory mechanisms; gives an overview on its roles in development, adult, and diseased retina; and elaborates on regulatory mechanisms under various conditions, such as hypoxia, oxidative stress, inflammation, and hyperthermia.

The chapter The RPE cell and the Immune System byDetrickandHookscovers the important role of the RPE in the innate immunity of the retina. Components of the innate immunity, such as toll-like receptors, cytokines, and complement, are introduced, and the role of the RPE in their interaction with microglia, in immune regulation, and in adaptive immune responses is described.

The RPE is involved in the development of different ocular diseases. In their chapter The RPE in Myopia Development,ZhangandWildsoetdescribe the role of the RPE in eye growth and refractive development, covering the changes of the RPE in high myopia and their part in regulation of eye size, elucidating on the role of different cytokines, neurotransmitters, and ion channels.

Dik,Bastiaans, andvan Meursaddress Retinal Pigment Epithelium in Proliferative Disorders, with the focus on the molecular regulation of the RPEs contribution to proliferative disease. In their chapter, after an introduction into the mechanisms of fibrosis in the retina, they elaborate on the epithelial mesenchymal transition and contributions of the RPE to inflammation as well as to angiogenesis.

In the chapter Retinal Pigment Epithelium in Health and Disease: Maturation, Aging and Age-Related Macular Degeneration,Ach,Tarau, andCurcioelaborate on the development, differentiation, and transdifferentiation of the RPE, stressing on alterations in adolescence and age as they present in the RPE, leading up to the changes seen in age-related macular degeneration (AMD).