Retina Metabolism and Metabolism in the Pigmented Epithelium: A Busy Intersection

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
James B. Hurley
Keyword(s):  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Science Volume ◽  
Annual Review ◽  
Publication Date ◽  
Outer Retina ◽  
Rpe Cells ◽  
Vision Science ◽  
Pigmented Epithelium ◽  
Capillary Bed

The outer retina is nourished from the choroid, a capillary bed just inside the sclera. O2, glucose, and other nutrients diffuse out of the choroid and then filter through a monolayer of retinal pigment epithelium (RPE) cells to fuel the retina. Recent studies of energy metabolism have revealed striking differences between retinas and RPE cells in the ways that they extract energy from fuels. The purpose of this review is to suggest and evaluate the hypothesis that the retina and RPE have complementary metabolic roles that make them depend on each other for survival and for their abilities to perform essential and specialized functions. Expected final online publication date for the Annual Review of Vision Science, Volume 7 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Best Practices for the Design of Clinical Trials Related to the Visual System

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Maureen G. Maguire
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Data Analysis ◽  
Best Practices ◽  
Visual System ◽  
Science Volume ◽  
Annual Review ◽  
Publication Date ◽  
Single Patient ◽  
Vision Science

Clinical trials for conditions affecting the visual system need to not only conform to the guidelines for all clinical trials, but also accommodate the possibility of both eyes of a single patient qualifying for the trial. In this review, I present the interplay of the key components in the design of a clinical trial, along with the modifications or options that may be available for trials addressing ocular conditions. Examples drawn from published reports of the design and results of clinical trials of ocular conditions are provided to illustrate application of the design principles. Current approaches to data analysis and reporting of trials are outlined, and the oversight and regulatory procedures to protect participants in clinical trials are discussed. Expected final online publication date for the Annual Review of Vision Science, Volume 7 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Coming of Age in Science: Just Look?

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ken Nakayama
Keyword(s):  
San Francisco ◽  
Coming Of Age ◽  
Science Volume ◽  
Annual Review ◽  
Publication Date ◽  
Vision Science ◽  
Common Space ◽  
Field Of Vision ◽  
The Times ◽  
Scientific Environment

With Professor Patrick Cavanagh, I started the Harvard Vision Sciences Laboratory in 1990. Blessed with the largesse of a wealthy university, we occupied a very large common space. Here, students pursued their own projects in a uniquely cooperative and exciting scientific environment. The times were just right in the emerging and expanding field of vision science. With good thesis projects under their belt, most of the students went on to successful careers. However, my own coming of age in science did not have such promising start. It only started well into my thirties when I joined the Smith Kettlewell Eye Research Institute in San Francisco. Providentially, it was there that I had the rare and unique opportunity to work closely and essentially only with peers (not students). Through these intense collaborations, I found my way as a scientist. Most of this account describes these formative years. Expected final online publication date for the Annual Review of Vision Science, Volume 7 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals A convenient protocol for establishing a human cell culture model of the outer retina.

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1107 ◽  
Author(s):  
Savannah A. Lynn ◽  
Eloise Keeling ◽  
Jennifer M. Dewing ◽  
David A. Johnston ◽  
Anton Page ◽  
...  
Keyword(s):  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Experimental Manipulation ◽  
Age Related Macular Degeneration ◽  
Attractive Alternative ◽  
Outer Retina ◽  
Rpe Cells ◽  
Age Related ◽  
Culture Model

The retinal pigment epithelium (RPE) plays a key role in the pathogenesis of several blinding retinopathies. Alterations to RPE structure and function are reported in Age-related Macular Degeneration, Stargardt and Best disease as well as pattern dystrophies. However, the precise role of RPE cells in disease aetiology remains incompletely understood. Many studies into RPE pathobiology have utilised animal models, which only recapitulate limited disease features. Some studies are also difficult to carry out in animals as the ocular space remains largely inaccessible to powerful microscopes. In contrast, in-vitro models provide an attractive alternative to investigating pathogenic RPE changes associated with age and disease. In this article we describe the step-by-step approach required to establish an experimentally versatile in-vitro culture model of the outer retina incorporating the RPE monolayer and supportive Bruch’s membrane (BrM). We show that confluent monolayers of the spontaneously arisen human ARPE-19 cell-line cultured under optimal conditions reproduce key features of native RPE. These models can be used to study dynamic, intracellular and extracellular pathogenic changes using the latest developments in microscopy and imaging technology. We also discuss how RPE cells from human foetal and stem-cell derived sources can be incorporated alongside sophisticated BrM substitutes to replicate the aged/diseased outer retina in a dish. The work presented here will enable users to rapidly establish a realistic in-vitro model of the outer retina that is amenable to a high degree of experimental manipulation which will also serve as an attractive alternative to using animals. This in-vitro model therefore has the benefit of achieving the 3Rs objective of reducing and replacing the use of animals in research. As well as recapitulating salient structural and physiological features of native RPE, other advantages of this model include its simplicity, rapid set-up time and unlimited scope for detailed single-cell resolution and matrix studies.

Remembering the Past to See the Future

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Nicole C. Rust ◽  
Stephanie E. Palmer
Keyword(s):  
Visual System ◽  
Science Volume ◽  
Annual Review ◽  
Publication Date ◽  
Brain Areas ◽  
Vision Science ◽  
The Past ◽  
Future Events ◽  
The Relationship

In addition to the role that our visual system plays in determining what we are seeing right now, visual computations contribute in important ways to predicting what we will see next. While the role of memory in creating future predictions is often overlooked, efficient predictive computation requires the use of information about the past to estimate future events. In this article, we introduce a framework for understanding the relationship between memory and visual prediction and review the two classes of mechanisms that the visual system relies on to create future predictions. We also discuss the principles that define the mapping from predictive computations to predictive mechanisms and how downstream brain areas interpret the predictive signals computed by the visual system. Expected final online publication date for the Annual Review of Vision Science, Volume 7 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Binocular Vision and Stereopsis Across the Animal Kingdom

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jenny C.A. Read
Keyword(s):  
Binocular Vision ◽  
Science Volume ◽  
Human Vision ◽  
Annual Review ◽  
Publication Date ◽  
Neural Basis ◽  
Animal Kingdom ◽  
Vision Science ◽  
The World ◽  
Vantage Points

Most animals have at least some binocular overlap, i.e., a region of space that is viewed by both eyes. This reduces the overall visual field and raises the problem of combining two views of the world, seen from different vantage points, into a coherent whole. However, binocular vision also offers many potential advantages, including increased ability to see around obstacles and increased contrast sensitivity. One particularly interesting use for binocular vision is comparing information from both eyes to derive information about depth. There are many different ways in which this might be done, but in this review, I refer to them all under the general heading of stereopsis. This review examines the different possible uses of binocular vision and stereopsis and compares what is currently known about the neural basis of stereopsis in different taxa. Studying different animals helps us break free of preconceptions stemming from the way that stereopsis operates in human vision and provides new insights into the different possible forms of stereopsis. Expected final online publication date for the Annual Review of Vision Science, Volume 7 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Visual Remapping

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Julie D. Golomb ◽  
James A. Mazer
Keyword(s):  
Receptive Fields ◽  
Science Volume ◽  
Neural Mechanisms ◽  
Annual Review ◽  
Publication Date ◽  
Multiple Forms ◽  
Vision Science ◽  
Open Questions ◽  
Object Features ◽  
Human Neuroimaging

Our visual system is fundamentally retinotopic. When viewing a stable scene, each eye movement shifts object features and locations on the retina. Thus, sensory representations must be updated, or remapped, across saccades to align presaccadic and postsaccadic inputs. The earliest remapping studies focused on anticipatory, presaccadic shifts of neuronal spatial receptive fields. Over time, it has become clear that there are multiple forms of remapping and that different forms of remapping may be mediated by different neural mechanisms. This review attempts to organize the various forms of remapping into a functional taxonomy based on experimental data and ongoing debates about forward versus convergent remapping, presaccadic versus postsaccadic remapping, and spatial versus attentional remapping. We integrate findings from primate neurophysiological, human neuroimaging and behavioral, and computational modeling studies. We conclude by discussing persistent open questions related to remapping, with specific attention to binding of spatial and featural information during remapping and speculations about remapping's functional significance. Expected final online publication date for the Annual Review of Vision Science, Volume 7 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

The Diversity of Eyes and Vision

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Dan-E. Nilsson
Keyword(s):  
Animal Behavior ◽  
Online Publication ◽  
Vision Research ◽  
Science Volume ◽  
Annual Review ◽  
Publication Date ◽  
Functional Constraints ◽  
Evolutionary Perspective ◽  
Vision Science ◽  
Eye Evolution

Every aspect of vision, from the opsin proteins to the eyes and the ways that they serve animal behavior, is incredibly diverse. It is only with an evolutionary perspective that this diversity can be understood and fully appreciated. In this review, I describe and explain the diversity at each level and try to convey an understanding of how the origin of the first opsin some 800 million years ago could initiate the avalanche that produced the astonishing diversity of eyes and vision that we see today. Despite the diversity, many types of photoreceptors, eyes, and visual roles have evolved multiple times independently in different animals, revealing a pattern of eye evolution strictly guided by functional constraints and driven by the evolution of gradually more demanding behaviors. I conclude the review by introducing a novel distinction between active and passive vision that points to uncharted territories in vision research. Expected final online publication date for the Annual Review of Vision Science, Volume 7 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals A human model of Batten disease shows role of CLN3 in phagocytosis at the photoreceptor–RPE interface

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Cynthia Tang ◽  
Jimin Han ◽  
Sonal Dalvi ◽  
Kannan Manian ◽  
Lauren Winschel ◽  
...  
Keyword(s):  
Photoreceptor Cell ◽  
Vision Loss ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Cell Loss ◽  
Human Model ◽  
Lysosomal Storage ◽  
Rpe Cells ◽  
Cln3 Disease

AbstractMutations in CLN3 lead to photoreceptor cell loss in CLN3 disease, a lysosomal storage disorder characterized by childhood-onset vision loss, neurological impairment, and premature death. However, how CLN3 mutations cause photoreceptor cell death is not known. Here, we show that CLN3 is required for phagocytosis of photoreceptor outer segment (POS) by retinal pigment epithelium (RPE) cells, a cellular process essential for photoreceptor survival. Specifically, a proportion of CLN3 in human, mouse, and iPSC-RPE cells localized to RPE microvilli, the site of POS phagocytosis. Furthermore, patient-derived CLN3 disease iPSC-RPE cells showed decreased RPE microvilli density and reduced POS binding and ingestion. Notably, POS phagocytosis defect in CLN3 disease iPSC-RPE cells could be rescued by wild-type CLN3 gene supplementation. Altogether, these results illustrate a novel role of CLN3 in regulating POS phagocytosis and suggest a contribution of primary RPE dysfunction for photoreceptor cell loss in CLN3 disease that can be targeted by gene therapy.

scholarly journals OCT imaging of rod mitochondrial respiration in vivo

2021 ◽  
pp. 153537022110137
Author(s):  
Bruce A Berkowitz ◽  
Haohua Qian
Keyword(s):  
Signaling Pathway ◽  
Mitochondrial Respiration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
The Body ◽  
Subretinal Space ◽  
Outer Retina ◽  
Water Efflux ◽  
Resolution Imaging

There remains a need for high spatial resolution imaging indices of mitochondrial respiration in the outer retina that probe normal physiology and measure pathogenic and reversible conditions underlying loss of vision. Mitochondria are involved in a critical, but somewhat underappreciated, support system that maintains the health of the outer retina involving stimulus-evoked changes in subretinal space hydration. The subretinal space hydration light–dark response is important because it controls the distribution of vision-critical interphotoreceptor matrix components, including anti-oxidants, pro-survival factors, ions, and metabolites. The underlying signaling pathway controlling subretinal space water management has been worked out over the past 30 years and involves cGMP/mitochondria respiration/pH/RPE water efflux. This signaling pathway has also been shown to be modified by disease-generating conditions, such as hypoxia or oxidative stress. Here, we review recent advances in MRI and commercially available OCT technologies that can measure stimulus-evoked changes in subretinal space water content based on changes in the external limiting membrane-retinal pigment epithelium region. Each step within the above signaling pathway can also be interrogated with FDA-approved pharmaceuticals. A highlight of these studies is the demonstration of first-in-kind in vivo imaging of mitochondria respiration of any cell in the body. Future examinations of subretinal space hydration are expected to be useful for diagnosing threats to sight in aging and disease, and improving the success rate when translating treatments from bench-to-bedside.

Advancing Socioeconomic Rights Through Interdisciplinary Factfinding: Opportunities and Challenges

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Sarah Knuckey ◽  
Joshua D. Fisher ◽  
Amanda M. Klasing ◽  
Tess Russo ◽  
Margaret L. Satterthwaite
Keyword(s):  
Human Rights ◽  
Mixed Methods ◽  
Social Science ◽  
Science Volume ◽  
Lessons Learned ◽  
Limited Resources ◽  
Annual Review ◽  
Publication Date ◽  
Socioeconomic Rights ◽  
Human Rights Movement

The human rights movement is increasingly using interdisciplinary, multidisciplinary, mixed-methods, and quantitative factfinding. There has been too little analysis of these shifts. This article examines some of the opportunities and challenges of these methods, focusing on the investigation of socioeconomic human rights. By potentially expanding the amount and types of evidence available, factfinding's accuracy and persuasiveness can be strengthened, bolstering rights claims. However, such methods can also present significant challenges and may pose risks in individual cases and to the human rights movement generally. Interdisciplinary methods can be costly in human, financial, and technical resources; are sometimes challenging to implement; may divert limited resources from other work; can reify inequalities; may produce “expertise” that disempowers rightsholders; and could raise investigation standards to an infeasible or counterproductive level. This article includes lessons learned and questions to guide researchers and human rights advocates considering mixed-methods human rights factfinding. Expected final online publication date for the Annual Review of Law and Social Science, Volume 17 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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