Article
Ophthalmology
Xufeng Dai, Xumin Jin, Qian Ye, Haixiao Huang, Lan Duo, Chunjie Lu, Jinhua Bao, Hao Chen
Summary: High expression of the RPE-specific RPE65 enzyme is crucial for generating 11-cis-retinal, a key component for vision. Deficiency in RPE65 can lead to severe retinal dysfunction, but early treatment with 11-cis-retinal in a mouse model shows promise in delaying cone degeneration and preserving retinal function.
EXPERIMENTAL EYE RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Carey Y. L. Huh, Henri Leinonen, Taylor Nakayama, Julia R. Tomasello, Jianye Zhang, Jack Zeitoun, John P. Peach, Maximilian Halabi, Jianying Z. Kiser, Krzysztof Palczewski, Philip D. Kiser, Sunil P. Gandhi
Summary: This study found that adult mice can recover visual responsiveness in the primary visual cortex following the correction of retinal defects through retinoid treatment. The treatment increases the number and amplitude of visually responsive neurons and restores the balance of eye-specific responses in the cortex. Additionally, it rescues the modulation of cortical responses by arousal.
Article
Multidisciplinary Sciences
Wenjing Wu, Yusuke Takahashi, Henry Younghwa Shin, Xiang Ma, Gennadiy Moiseyev, Jian-Xing Ma
Summary: The D477G mutation of retinal pigment epithelium (RPE)65 affects visual chromophore regeneration and retinal structure, highlighting the importance of the light environment in its pathogenicity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Julio C. Corral-Serrano, Paul E. Sladen, Daniele Ottaviani, Olivia F. Rezek, Dimitra Athanasiou, Katarina Jovanovic, Jacqueline van der Spuy, Brian C. Mansfield, Michael E. Cheetham
Summary: This study demonstrates the potential therapeutic effect of eupatilin on CEP290-associated retinal diseases. Eupatilin improves cilia formation and length, reduces rhodopsin retention, and modulates gene expression in retinal organoids.
Article
Biotechnology & Applied Microbiology
Albert M. Maguire, Jean Bennett, Elena M. Aleman, Bart P. Leroy, Tomas S. Aleman
Summary: Luxturna, the first FDA-approved gene therapy product for a genetic disease, has reversed blindness in individuals with retinal degenerative disease. It has not only transformed the lives of many previously destined to live a life of blindness, but also sparked interest in developing gene therapy treatments for other inherited retinal diseases.
Article
Multidisciplinary Sciences
Samuel G. Jacobson, Artur Cideciyan, Allen C. Ho, Igor Peshenko, Alexandra Garafalo, Alejandro J. Roman, Alexander Sumaroka, Vivian Wu, Arun K. Krishnan, Rebecca Sheplock, Sanford L. Boye, Alexander M. Dizhoor, Shannon E. Boye
Summary: The ongoing first-in-human clinical trial of gene therapy for Leber congenital amaurosis due to mutations in the GUCY2D gene has shown promising early results, demonstrating safety and efficacy in both rod and cone photoreceptor function.
Review
Physiology
Rick H. Cote
Summary: This review article discusses the role of cGMP in the visual signaling pathway of the vertebrate retina, particularly focusing on the metabolism of cGMP in rod and cone photoreceptors. It highlights recent advances in understanding the structural and conformational changes involved in the activation of PDE6 by transducin and the regulation of its lifetime, as well as the potential therapeutic applications of pharmacological compounds targeting PDE6 in inherited retinal diseases.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Gustavo D. Aguirre, Artur Cideciyan, Valerie L. Dufour, Ana Ripolles-Garcia, Raghavi Sudharsan, Malgorzata Swider, Roman Nikonov, Simone Iwabe, Sanford L. Boye, William W. Hauswirth, Samuel G. Jacobson, William A. Beltran
Summary: Gene therapy using AAV-mediated NPHP5 gene augmentation successfully restores photoreceptor structure, function, and vision in a canine model of Leber congenital amaurosis, offering a potential path for translation to human treatment.
Article
Multidisciplinary Sciences
Michihiko Aramaki, Xuefeng Wu, Hong Liu, Ye Liu, Young-Wook Cho, Mina Song, Yulong Fu, Lily Ng, Douglas Forrest
Summary: Cone photoreceptor diversity is crucial for color vision, but little is known about the control of diversity in these neurons. In this study, the researchers derived a Cre driver to isolate individual M and S opsin-enriched cones in mice and identified expression gradients for groups of genes. They found that thyroid hormone receptor ss 2 (TR ss 2) plays a role in controlling the expression of these genes and promoting cone diversity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Genetics & Heredity
Isabelle Perrault, Sylvain Hanein, Xavier Gerard, Nelson Mounguengue, Ryme Bouyakoub, Mohammed Zarhrate, Cecile Fourrage, Fabienne Jabot-Hanin, Beatrice Bocquet, Isabelle Meunier, Xavier Zanlonghi, Josseline Kaplan, Jean-Michel Rozet
Summary: This study investigates the non-coding regions of a non-syndromic LCA gene, identifying the most frequent disease allele.
Article
Neurosciences
Annia Abtout, Gordon Fain, Jurgen Reingruber
Summary: This study analyzed the contribution of various biological processes in the photoreceptor light response, finding that the shape of the response is controlled by deactivation parameters, while activation parameters scale the shape and affect the amplitude. The rising phase of the response is shown to depend on Ca2+ feedback, contrary to previous belief. New methods were devised to extract activation and deactivation rates from the analysis of response shape and amplitude.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Review
Biochemistry & Molecular Biology
Nicole C. L. Noel, Ian M. MacDonald, W. Ted Allison
Summary: Zebrafish are instrumental in generating models for photoreceptor degeneration, providing insights into causes and treatments of photoreceptor diseases. These models offer detailed information and important insights for disease research and therapeutic approaches.
Review
Genetics & Heredity
Chu-Hsuan Huang, Chung-May Yang, Chang-Hao Yang, Yu-Chih Hou, Ta-Ching Chen
Summary: Leber's congenital amaurosis (LCA) is a severe genetic retinal disease responsible for 20% of childhood blindness, with its genetic background widely understood and disease-causing variants identified in 38 genes. Different pathogenetic mechanisms result in dysfunction or absence of encoded proteins in the visual cycle, leading to extensive heterogeneity in clinical phenotypes. Gene therapy shows promise in managing LCA, with ongoing clinical trials focusing on common disease-causing genes such as RPE65.
Article
Neurosciences
Matthew A. Smith, David A. Waugh, Denise L. McBurney, John C. George, Robert S. Suydam, Johannes G. M. Thewissen, Samuel D. Crish
Summary: This study identified two novel cone morphologies in the bowhead whale and beluga retina, and revealed the presence of proteins related to magnetosensation in these structures. These findings underscore the unique evolutionary development of cone and retinal anatomy in cetaceans, and suggest a potential functional reallocation of these cells.
JOURNAL OF COMPARATIVE NEUROLOGY
(2021)
Article
Cell Biology
Matthew J. Annear, Freya M. Mowat, Laurence M. Occelli, Alexander J. Smith, Paul G. Curran, James W. Bainbridge, Robin R. Ali, Simon M. Petersen-Jones
Summary: The Rpe65-deficient dog model has been crucial for studying LCA2 translational therapies. This study provided a comprehensive report on the natural history of retinal changes in this model, showing age-related decline in retinal sensitivity and thickness. The findings suggest that photoreceptor loss leads to vision impairment, but some desensitized photoreceptors may still exist in older dogs.
Article
Biology
Jingjing Zang, Matthias Gesemann, Jennifer Keim, Marijana Samardzija, Christian Grimm, Stephan C. F. Neuhauss
Summary: The study found that the circadian rhythm influences the expression and function of visual transduction cascade regulators in diurnal zebrafish and nocturnal mice, impacting their visual abilities and photoresponse kinetics. Additionally, the rhythmicity of these regulators persists in continuous darkness and is disrupted by an inverted light cycle and constant light exposure.
Article
Biology
Duygu Karademir, Vyara Todorova, Lynn J. A. Ebner, Marijana Samardzija, Christian Grimm
Summary: This study utilizes droplet-based single-cell RNA sequencing to investigate the degeneration process in rod and cone photoreceptor cells in an RP mouse model. The results identify early changes in rods and potential early responses in cones, suggesting mechanisms involved in secondary cone degeneration. Furthermore, the study implicates EGR1 as a potential key regulator of early degenerative events in both types of photoreceptor cells.
Article
Biochemistry & Molecular Biology
Florian Peters, Lynn J. A. Ebner, David Atac, Jordi Maggi, Wolfgang Berger, Anneke den Hollander, Christian Grimm
Summary: This study focuses on analyzing the dysregulation of ATP-binding cassette transporter A1 (ABCA1) in induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) cells. The results show that genetic variations associated with age-related macular degeneration (AMD) result in increased ABCA1 gene expression, reduced cholesterol efflux, and increased lipid accumulation. Additionally, hypoxia decreases ABCA1 expression and increases intracellular lipid accumulation. Stimulating ABCA1 expression could improve RPE cell survival and reduce the risk of developing AMD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Annie L. Miller, Paula Fuller-Carter, Klaudija Masarini, Marijana Samardzija, Kim W. Carter, Rabab Rashwan, Xin Ru Lim, Alicia A. Brunet, Abha Chopra, Ramesh Ram, Christian Grimm, Marius Ueffing, Livia S. Carvalho, Dragana Trifunovic
Summary: Inherited retinal diseases (IRDs) are a group of blinding disorders that affect the cone and rod photoreceptors. This study explores the potential therapeutic benefits of a histone demethylase inhibitor, GSK-J4, on cone cell survival in a mouse model of achromatopsia. The results suggest that epigenetic modulation of histones may be a promising approach in slowing down cone degeneration in IRDs.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Neurosciences
Divya Ail, Marijana Samardzija, Andy C. M. Chang, Jadwiga Keck, Roger R. Reddel, Christian Grimm
Summary: This study investigated the expression of stanniocalcins in the retina and found that Stc2 was induced in acute and chronic hypoxia models, regulated by HIF1, while Stc1 remained stable. Furthermore, Stc2 was expressed in the inner retina, rather than in photoreceptors.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Eva Kiessling, Florian Peters, Lynn J. A. Ebner, Luca Merolla, Marijana Samardzija, Matthias R. Baumgartner, Christian Grimm, Sean Froese
Summary: The MMACHC gene encodes an enzyme involved in vitamin B12 metabolism. Oxidative stress may impair vitamin B12 metabolism by suppressing MMACHC expression.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2022)
Article
Neurosciences
Lew Kaplan, Corinne Drexler, Anna M. Pfaller, Santra Brenna, Kirsten A. Wunderlich, Andrea Dimitracopoulos, Juliane Merl-Pham, Maria-Theresa Perez, Ursula Schloetzer-Schrehardt, Volker Enzmann, Marijana Samardzija, Berta Puig, Peter Fuchs, Kristian Franze, Stefanie M. Hauck, Antje Grosche
Summary: This study revealed the expression profiles of cone- and rod-associated Muller cells in the human macula and identified pathways related to extracellular matrix and cell adhesion. EPPK1 was highly expressed in macular Muller cells and played a role in intermediate filament organization. Knockout of EPPK1 in a human Muller cell-derived cell line resulted in changes in cell size, shape, and filopodia characteristics. Therefore, EPPK1 is a central molecular player in the region-specific architecture of the human retina, enabling specific functions under mechanical loads in vivo.
Article
Multidisciplinary Sciences
Vyara Todorova, Luca Merolla, Duygu Karademir, Gabriele M. Wogenstein, Julian Behr, Lynn J. A. Ebner, Marijana Samardzija, Christian Grimm
Summary: Understanding the physiology of the retina, particularly the highly polarized photoreceptors, is crucial for advancing our knowledge of normal vision processes and developing effective therapies for retinal degenerative diseases. However, studying the molecular mechanisms of photoreceptors is challenging due to the heterogeneity of retinal tissue and the lack of reliable cell separation methods. In this study, the researchers present a simple technique called ReLayS that successfully separates different parts of photoreceptors, enabling protein and RNA analysis. The method was validated using known proteins and genes and also revealed light-driven translocation of transducin.
SCIENTIFIC REPORTS
(2022)
Article
Neurosciences
Vyara Todorova, Mia Fee Stauffacher, Luca Ravotto, Sarah Notzli, Duygu Karademir, Lynn J. A. Ebner, Cornelia Imsand, Luca Merolla, Stefanie. M. M. Hauck, Marijana Samardzija, Aiman. S. S. Saab, L. Felipe Barros, Bruno Weber, Christian Grimm
Summary: This study investigates the pathological mechanisms of photoreceptor (PR) degeneration during chronic activation of hypoxia-inducible factors (HIFs). The results show that PR cells have an exceptionally high glycolytic flux and the activation of HIFs slows down the cellular anabolism, leading to the shortening of rod outer segments before cell degeneration.
MOLECULAR NEURODEGENERATION
(2023)