No abstract

The retinal pigment epithelium is a fundamental component of the retina that plays essential roles in visual functions. Damage to the structure and function of the retinal pigment epithelium leads to a variety of retinopathies, and there is currently no curative therapy for these disorders. Therefore, studying the relationship between the development, function, and pathobiology of the retinal pigment epithelium is important for the prevention and treatment of retinopathies. Here we review the function of the retinal pigment epithelium and its relevance to the pathobiology, and discuss potential strategies for the treatment of retinopathies. In doing so, we provide new viewpoints outlining new ideas for the future study and treatment of retinopathies.

The microtubule cytoskeleton plays a critical role in a wide range of cellular activities and has been shown to be a highly effective target for the treatment of human malignancies. Despite the recent focus on proteomics and high-throughput profiling, it is clear that analysis of plant extracts has yielded several highly efficacious microtubule-targeting agents (MTAs) currently in clinical use, as well as agents in the current pipeline with promising efficacy. To date, a large proportion of the world’s plant biodiversity remains untapped by the pharmaceutical industry, presenting a major opportunity for the discovery of novel pharmacologically active lead compounds. Because plants contain an astonishing array of structurally diverse molecules, they represent an ideal source for the discovery of novel MTA leads. To demonstrate the importance of searching for novel bioactive compounds across the plant kingdom, herein, we summarize the discovery and development of plant-derived MTAs and discuss the challenges associated with searching for novel bioactive compounds from plants. We propose potential solutions to these problems with the aim of facilitating further exploration and identification of novel MTAs from plant biodiversity.

Orientation and positioning of the mitotic spindle are involved in dictating cell division axis and cleavage site, and play important roles in cell fate determination and tissue morphogenesis. However, how spindle movement is controlled to achieve a defined alignment within the dividing cell is not fully understood. Here, we describe an unexpected role for apoptosis signal-regulating kinase 1 (ASK1) in regulating spindle behavior. We find that ASK1 is required for proper mitotic progression and daughter cell adhesion to the substratum. ASK1 interacts with end-binding protein 1 (EB1) and phosphorylates EB1 at serine 40, threonine 154 and threonine 206, enhancing its binding to the plus ends of astral microtubules. Consequently, astral microtubules are stabilized and therefore capable of mediating spindle interaction with the cell cortex, a requirement for spindle movement. These findings reveal a previously undiscovered function of ASK1 in cell division by regulating spindle orientation and positioning, and point to the importance of protein phosphorylation in the regulation of spindle behavior.