Catherine Bowes Rickman

Bio: Catherine Bowes Rickman is an academic researcher from Duke University. The author has contributed to research in topics: Macular degeneration & Retinal pigment epithelium. The author has an hindex of 30, co-authored 56 publications receiving 3394 citations. Previous affiliations of Catherine Bowes Rickman include University of Hamburg & University of Iowa.

Dysregulated autophagy in the RPE is associated with increased susceptibility to oxidative stress and AMD.

Abstract: Autophagic dysregulation has been suggested in a broad range of neurodegenerative diseases including age-related macular degeneration (AMD). To test whether the autophagy pathway plays a critical role to protect retinal pigmented epithelial (RPE) cells against oxidative stress, we exposed ARPE-19 and primary cultured human RPE cells to both acute (3 and 24 h) and chronic (14 d) oxidative stress and monitored autophagy by western blot, PCR, and autophagosome counts in the presence or absence of autophagy modulators. Acute oxidative stress led to a marked increase in autophagy in the RPE, whereas autophagy was reduced under chronic oxidative stress. Upregulation of autophagy by rapamycin decreased oxidative stress-induced generation of reactive oxygen species (ROS), whereas inhibition of autophagy by 3-methyladenine (3-MA) or by knockdown of ATG7 or BECN1 increased ROS generation, exacerbated oxidative stress-induced reduction of mitochondrial activity, reduced cell viability, and increased lipofuscin. Exam...

Unraveling a multifactorial late-onset disease: from genetic susceptibility to disease mechanisms for age-related macular degeneration.

Abstract: Aging-associated neurodegenerative diseases significantly influence the quality of life of affected individuals. Genetic approaches, combined with genomic technology, have provided powerful insights into common late-onset diseases, such as age-related macular degeneration (AMD). Here, we discuss current findings on the genetics of AMD to highlight areas of rapid progress and new challenges. We also attempt to integrate available genetic and biochemical data with cellular pathways involved in aging to formulate an integrated model of AMD pathogenesis.

Dry age-related macular degeneration: mechanisms, therapeutic targets, and imaging.

Abstract: Age-related macular degeneration is the leading cause of irreversible visual dysfunction in individuals over 65 in Western Society. Patients with AMD are classified as having early stage disease (early AMD), in which visual function is affected, or late AMD (generally characterized as either “wet” neovascular AMD, “dry” atrophic AMD or both), in which central vision is severely compromised or lost. Until recently, there have been no therapies available to treat the disorder(s). Now, the most common wet form of late-stage AMD, choroidal neovascularization, generally responds to treatment with anti–vascular endothelial growth factor therapies. Nevertheless, there are no current therapies to restore lost vision in eyes with advanced atrophic AMD. Oral supplementation with the Age-Related Eye Disease Study (AREDS) or AREDS2 formulation (antioxidant vitamins C and E, lutein, zeaxanthin, and zinc) has been shown to reduce the risk of progression to advanced AMD, although the impact was in neovascular rather than atrophic AMD. Recent findings, however, have demonstrated several features of early AMD that are likely to be druggable targets for treatment. Studies have established that much of the genetic risk for AMD is associated with complement genes. Consequently, several complement-based therapeutic treatment approaches are being pursued. Potential treatment strategies against AMD deposit formation and protein and/or lipid deposition will be discussed, including anti-amyloid therapies. In addition, the role of autophagy in AMD and prevention of oxidative stress through modulation of the antioxidant system will be explored. Finally, the success of these new therapies in clinical trials and beyond relies on early detection, disease typing, and predicting disease progression, areas that are currently being rapidly transformed by improving imaging modalities and functional assays.

Minimal information for studies of extracellular vesicles 2018 (MISEV2018) : a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

Abstract: The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

Complement: a key system for immune surveillance and homeostasis

Abstract: Nearly a century after the significance of the human complement system was recognized, we have come to realize that its functions extend far beyond the elimination of microbes. Complement acts as a rapid and efficient immune surveillance system that has distinct effects on healthy and altered host cells and foreign intruders. By eliminating cellular debris and infectious microbes, orchestrating immune responses and sending 'danger' signals, complement contributes substantially to homeostasis, but it can also take action against healthy cells if not properly controlled. This review describes our updated view of the function, structure and dynamics of the complement network, highlights its interconnection with immunity at large and with other endogenous pathways, and illustrates its multiple roles in homeostasis and disease.

Repertoires of Autophagy in the Pathogenesis of Ocular Diseases

Abstract: Autophagy is an important intracellular degradative process that delivers cytoplasmic proteins to lysosome for degradation. Dysfunction of autophagy is implicated in several human diseases, such as neurodegenerative diseases, infectious diseases, and cancers. Autophagy-related proteins are constitutively expressed in the eye. Increasing studies have revealed that abnormal autophagy is an important pathological feature of several ocular diseases. Pharmacological manipulation of autophagy may provide an alternative therapeutic target for some ocular diseases. In this manuscript, we reviewed the relevant progress about the role of autophagy in the pathogenesis of ocular diseases.

The Retinal Pigment Epithelium in Visual Function

Abstract: Located between vessels of the choriocapillaris and light-sensitive outer segments of the photoreceptors, the retinal pigment epithelium (RPE) closely interacts with photoreceptors in the maintenance of visual function. Increasing knowledge of the multiple functions performed by the RPE improved the understanding of many diseases leading to blindness. This review summarizes the current knowledge of RPE functions and describes how failure of these functions causes loss of visual function. Mutations in genes that are expressed in the RPE can lead to photoreceptor degeneration. On the other hand, mutations in genes expressed in photoreceptors can lead to degenerations of the RPE. Thus both tissues can be regarded as a functional unit where both interacting partners depend on each other.