Article
Multidisciplinary Sciences
Dianlei Guo, Jiali Ru, Lijing Xie, Mingjuan Wu, Yingchun Su, Shiyong Zhu, Shujuan Xu, Bin Zou, Yanhong Wei, Xialin Liu, Yizhi Liu, Chunqiao Liu
Summary: The study discovered that Tmem138 plays a crucial role in the functional organization of photoreceptor connecting cilium (CC), which is essential for rhodopsin localization and outer segment (OS) biogenesis. Inactivation of Tmem138 leads to abnormal development of OS and degeneration of photoreceptor cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biology
Yeming Yang, Ping Shuai, Xiao Li, Kuanxiang Sun, Xiaoyan Jiang, Wenjing Liu, Weidong Le, Haisong Jiang, Yuping Liu, Xianjun Zhu
Summary: The study demonstrates that Mettl14 plays a crucial role in regulating phototransduction and ciliogenesis events, essential for photoreceptor function and survival, highlighting the importance of m6A modification in visual function.
Article
Biochemistry & Molecular Biology
Miriam Ryl, Alexander Urbasik, Kaspar Gierke, Norbert Babai, Anneka Joachimsthaler, Andreas Feigenspan, Renato Frischknecht, Nina Stallwitz, Anna Fejtova, Jan Kremers, Julia von Wittgenstein, Johann Helmut Brandstaetter
Summary: The study investigated the impact of mutations in the Bassoon protein on the synaptic function and structure of photoreceptor cells in mice. Results showed that the synaptic defects were more severe in Bsn(gt/gt) mice, while expression of the Bsn(gt) allele led to cone photoreceptor death and neurite sprouting in the outer retina.
Article
Neurosciences
Jillian N. Pearring, Jorge Martinez-Marquez, Jason R. Willer, Eric C. Lieu, Raquel Y. Salinas, Vadim Y. Arshavsky
Summary: The study found that the targeted delivery of the rod cyclic nucleotide-gated (CNG) channel to the outer segment uses the conventional secretory pathway and requires preassembly of its constituent alpha 1 and beta 1 subunits. The N-terminal glutamic acid-rich protein domain of CNG beta 1 encodes specific information targeting the channel to rod outer segments and connects the channel to photoreceptor disk rims through an interaction with peripherin-2. These findings reveal fine functional specializations within the CNG channel's structural domains and suggest that its sequestration to the outer segment plasma membrane requires an interaction with peripherin-2.
JOURNAL OF NEUROSCIENCE
(2021)
Review
Ophthalmology
Imran H. Yusuf, Andrew M. Garrett, Robert E. MacLaren, Peter Charbel Issa
Summary: Cadherins are a superfamily of intercellular adhesion molecules that play important roles in tissue morphogenesis, neural circuit formation, and maintenance of the retina. Mutations in genes encoding cadherins have been identified as causes of inherited retinal degeneration. This review summarizes the classification and function of cadherins in the inner and outer retina, and provides an overview of the molecular genetics and clinical phenotypes of monogenic retinal cadherinopathies.
PROGRESS IN RETINAL AND EYE RESEARCH
(2022)
Review
Cell Biology
Holly Y. Chen, Ryan A. Kelley, Tiansen Li, Anand Swaroop
Summary: The primary cilium is a microtubule-based organelle that senses external environment and modulates diverse signaling pathways in different cell types and tissues; ciliopathies are a spectrum of clinical entities caused by aberrant ciliogenesis or ciliary transport, leading to overlapping yet highly variable phenotypes; dysfunction and degeneration of light sensing photoreceptors in the retina are highly penetrant in ciliopathies.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Laura Sanchez-Bellver, Vasileios Toulis, Gemma Marfany
Summary: Ciliopathies are a group of heterogeneous inherited disorders caused by dysfunction of the cilium, affecting cells in multiple organs. The unique feature of daily renewal in photoreceptor outer segments and the efficient transport of proteins in ciliary transport are crucial for photoreceptor survival.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Developmental Biology
Sumitha Prameela Bharathan, Angela Ferrario, Kayla Stepanian, G. Esteban Fernandez, Mark W. Reid, Justin S. Kim, Chloe Hutchens, Narine Harutyunyan, Carolyn Marks, Matthew E. Thornton, Brendan H. Grubbs, David Cobrinik, Jennifer G. Aparicio, Aaron Nagiel
Summary: This study establishes a pseudo-temporal staging system for the development of the first synapse in the visual system in the human retina, termed OPL-Stages 0 to 4. By studying the maturation and organization of photoreceptors, depolarizing bipolar cells, and horizontal cells, the study validates this staging system through precise subcellular localization analysis of bassoon. Additionally, the study demonstrates the utility of human retinal organoids (HROs) derived from human embryonic and induced pluripotent stem cells in replicating key aspects of human photoreceptor-bipolar cell synaptogenesis in vitro.
Article
Neurosciences
Kennedy Bolstad, Inigo Novales Flamarique
Summary: Fishes can quickly modulate their photoreceptor properties to optimize visual function in response to different light environments. In this study, Atlantic halibut larvae and juveniles exposed to blue light showed changes in cone opsin gene expression and photoreceptor structure, indicating rapid plasticity as a function of developmental stage. These adjustments help the fish perceive achromatic or chromatic contrasts in accordance with their ecological needs.
JOURNAL OF COMPARATIVE NEUROLOGY
(2023)
Article
Medicine, Research & Experimental
Sophia Grotz, Jessica Schaefer, Kirsten A. Wunderlich, Zdenka Ellederova, Hannah Auch, Andrea Baehr, Petra Runa-Vochozkova, Janet Fadl, Vanessa Arnold, Taras Ardan, Miroslav Veith, Gianluca Santamaria, Georg Dhom, Wolfgang Hitzl, Barbara Kessler, Christian Eckardt, Joshua Klein, Anna Brymova, Joshua Linnert, Mayuko Kurome, Valeri Zakharchenko, Andrea Fischer, Andreas Blutke, Anna Doering, Stepanka Suchankova, Jiri Popelar, Eduardo Rodriguez-Bocanegra, Julia Dlugaiczyk, Hans Straka, Helen May-Simera, Weiwei Wang, Karl-Ludwig Laugwitz, Luk H. Vandenberghe, Eckhard Wolf, Kerstin Nagel-Wolfrum, Tobias Peters, Jan Motlik, M. Dominik Fischer, Uwe Wolfrum, Nikolai Klymiuk
Summary: This study generated the first translational animal model for Usher syndrome type 1, which exhibits characteristics of hearing loss, vestibular dysfunction, and visual impairment similar to human patients. The research also confirmed the therapeutic potential of gene repair and gene therapy for Usher syndrome through in vitro assessments using primary cells from Usher syndrome pigs or patients.
EMBO MOLECULAR MEDICINE
(2022)
Review
Biology
Arupratan Das, Yoshikazu Imanishi
Summary: This review discusses targets and drug discovery strategies for inherited retinal degeneration using animal models, stem cells, and small molecule screening, with updates on preclinical developments. Inherited retinal degeneration is a group of devastating blinding disorders for which no cures exist. The review also highlights the potential of modulating metabolic pathways and utilizing phenotypic screening in therapeutic approaches, as well as the use of stem cell-based disease models for drug discovery and preclinical development.
Article
Ophthalmology
Vasily M. Smirnov, Marco Nassisi, Saddek Mohand-Said, Crystel Bonnet, Anne Aubois, Celine Devisme, Thilissa Dib, Christina Zeitz, Natalie Loundon, Sandrine Marlin, Christine Petit, Bahram Bodaghi, Jose-Alain Sahel, Isabelle Audo
Summary: This study provides a detailed phenotypic description of rod-cone dystrophy associated with CLRN1 variants. The retinal phenotype includes visual acuity loss, visual field constriction, and retinal degeneration. Four pathogenic variants were identified in the study.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Pharmacology & Pharmacy
Daowei Zhang, Jiawen Wu, Jihong Wu, Shenghai Zhang
Summary: The study found that Pae treatment can reduce apoptosis of LD-induced RP cells and increase cell viability and autophagy in 661W cells. Pae enhances cell antioxidant capacity and protects retinal function by regulating autophagy pathways.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Abirami Santhanam, Eyad Shihabeddin, Haichao Wei, Jiaqian Wu, John O'Brien
Summary: This study analyzed single-cell transcriptome data from zebrafish retina to understand the transcriptional changes in different cell types in a model of retinitis pigmentosa. The study found that oxidative stress is widespread throughout the retina, affecting various cell types and leading to an increase in oxidative metabolism and glycolysis. There was also evidence of synaptic remodeling and enhanced glutamatergic transmission in the inner retina. Additionally, changes in circadian rhythm regulation and the transcriptomic signatures of retinal progenitor cells and newly formed rods were identified.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Multidisciplinary Sciences
Dongliang Liu, Dandan Qian, Huaizong Shen, Deshun Gong
Summary: A study reported the structural characteristics of human Meckelin, including a unique protein folding pattern and a stable homodimer structure, providing a basis for further exploration of the function and disease mechanisms of Meckelin.
Article
Multidisciplinary Sciences
Avigail Beryozkin, Chen Matsevich, Alexey Obolensky, Corinne Kostic, Yvan Arsenijevic, Uwe Wolfrum, Eyal Banin, Dror Sharon
Summary: Research findings indicate that FAM161A mutations are the most common cause of inherited retinal degenerations in Israel. A knockout mouse model lacking the major exon #3 of Fam161a showed gradual retinal degeneration over time, including thinning of the retina and changes in autofluorescence pigments. This model may be utilized for gene therapy treatments in the future.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Rachel E. Turn, Joshua Linnert, Eduardo D. Gigante, Uwe Wolfrum, Tamara Caspary, Richard A. Kahn
Summary: ELMOD2 is a GTPase-activating protein with broad specificity for ARF family GTPases, involved in various cellular processes including ciliary morphology and signaling. Functional links exist between ELMOD2, ARL2, and Rootletin, acting together in a pathway to suppress spurious ciliation and maintain centrosome cohesion. These proteins act downstream of TTBK2 and upstream of CP110 to regulate ciliary licensing.
MOLECULAR BIOLOGY OF THE CELL
(2021)
Article
Multidisciplinary Sciences
Deva K. Kusuluri, Baran E. Gueler, Barbara Knapp, Nicola Horn, Karsten Boldt, Marius Ueffing, Gabriela Aust, Uwe Wolfrum
Summary: VLGR1, the largest adhesion G protein-coupled receptor in humans, is associated with diseases like deaf blindness and epilepsy. Research shows that the localization and assembly of VLGR1 in focal adhesions play a critical role in cell spread, migration, and response to mechanical stretch.
Article
Biochemistry & Molecular Biology
Adem Yildirim, Sina Mozaffari-Jovin, Ann-Kathrin Wallisch, Jessica Schafer, Sebastian E. J. Ludwig, Henning Urlaub, Reinhard Luhrmann, Uwe Wolfrum
Summary: The study reveals molecular links between the SANS protein and the spliceosome in catalyzing pre-mRNA splicing in the nucleus. SANS is found in Cajal bodies and nuclear speckles, where it plays a key role in transporting tri-snRNPs and in spliceosome assembly. Depletion of SANS alters the kinetics of spliceosome assembly, leading to accumulation of complex A.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Cell Biology
Rachel E. Turn, Yihan Hu, Skylar Dewees, Narra Devi, Michael P. East, Katherine R. Hardin, Tala Khatib, Joshua Linnert, Uwe Wolfrum, Michael J. Lim, James E. Casanova, Tamara Caspary, Richard A. Kahn
Summary: ELMODs are a family of proteins that regulate the activity of a variety of GTPases. This study investigated the functions of ELMOD1 and ELMOD3 and compared them to the functions of ELMOD2. Deletion of ELMOD1 or ELMOD3 resulted in impaired primary cilium formation and protein trafficking from the Golgi to cilia. These phenotypes were reversed by activating mutant expression of ARL3 or ARL16.
MOLECULAR BIOLOGY OF THE CELL
(2022)
Article
Medicine, Research & Experimental
Sophia Grotz, Jessica Schaefer, Kirsten A. Wunderlich, Zdenka Ellederova, Hannah Auch, Andrea Baehr, Petra Runa-Vochozkova, Janet Fadl, Vanessa Arnold, Taras Ardan, Miroslav Veith, Gianluca Santamaria, Georg Dhom, Wolfgang Hitzl, Barbara Kessler, Christian Eckardt, Joshua Klein, Anna Brymova, Joshua Linnert, Mayuko Kurome, Valeri Zakharchenko, Andrea Fischer, Andreas Blutke, Anna Doering, Stepanka Suchankova, Jiri Popelar, Eduardo Rodriguez-Bocanegra, Julia Dlugaiczyk, Hans Straka, Helen May-Simera, Weiwei Wang, Karl-Ludwig Laugwitz, Luk H. Vandenberghe, Eckhard Wolf, Kerstin Nagel-Wolfrum, Tobias Peters, Jan Motlik, M. Dominik Fischer, Uwe Wolfrum, Nikolai Klymiuk
Summary: This study generated the first translational animal model for Usher syndrome type 1, which exhibits characteristics of hearing loss, vestibular dysfunction, and visual impairment similar to human patients. The research also confirmed the therapeutic potential of gene repair and gene therapy for Usher syndrome through in vitro assessments using primary cells from Usher syndrome pigs or patients.
EMBO MOLECULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Barbara Knapp, Jens Roedig, Heiko Roedig, Jacek Krzysko, Nicola Horn, Baran E. Gueler, Deva Krupakar Kusuluri, Adem Yildirim, Karsten Boldt, Marius Ueffing, Ines Liebscher, Uwe Wolfrum
Summary: In this study, novel protein networks and functional cellular modules associated with VLGR1 were identified using affinity proteomics. The findings provide new insights into the possible functions of VLGR1, related to the development of Usher syndrome, epilepsy, and other neuronal diseases.
Article
Biochemistry & Molecular Biology
Kerstin Nagel-Wolfrum, Benjamin R. Fadl, Mirjana M. Becker, Kirsten A. Wunderlich, Jessica Schaefer, Daniel Sturm, Jacques Fritze, Burcu Guer, Lew Kaplan, Tommaso Andreani, Tobias Goldmann, Matthew Brooks, Margaret R. Starostik, Anagha Lokhande, Melissa Apel, Karl R. Fath, Katarina Stingl, Susanne Kohl, Margaret M. DeAngelis, Ursula Schlotzer-Schrehardt, Ivana K. Kim, Leah A. Owen, Jan M. Vetter, Norbert Pfeiffer, Miguel A. Andrade-Navarro, Antje Grosche, Anand Swaroop, Uwe Wolfrum
Summary: Usher syndrome (USH) is a common genetic disorder causing deaf-blindness. This study explores the role of harmonin protein in the pathophysiology of USH1C in the human eye. The localization and expression of harmonin in various retinal cells are correlated with the clinical phenotype observed in USH1C patients. Additionally, the study shows the potential of using harmonin_a1 transcript isoform for gene therapy treatment in USH1C patients.
HUMAN MOLECULAR GENETICS
(2023)
Article
Cell Biology
Jacek Krzysko, Filip Maciag, Anna Mertens, Baran Enes Gueler, Joshua Linnert, Karsten Boldt, Marius Ueffing, Kerstin Nagel-Wolfrum, Martin Heine, Uwe Wolfrum
Summary: This study reveals the molecular and functional interaction between VLGR1 and MAMs, highlighting the essential role of VLGR1 in the regulation of Ca2+ homeostasis.
Article
Cell Biology
Romy Winkler, Marianne Quaas, Stefan Glasmacher, Uwe Wolfrum, Torsten Thalheim, Joerg Galle, Knut Krohn, Thomas M. Magin, Gabriela Aust
Summary: The expression and function of GPR115 in skin, specifically in epidermal differentiation, has been largely unknown. This study reveals that GPR115 is present in a small subset of keratinocytes in the stratified epidermis, and its expression is delayed in psoriatic skin. Deletion of GPR115 leads to reduced keratinocyte stratification, suggesting its role in epidermal differentiation. Intriguingly, endogenous GPR115 localizes along keratin filaments in a regular pattern, indicating a previously unknown function in regulating epidermal differentiation and keratin expression.
Article
Pharmacology & Pharmacy
Baran E. Gueler, Joshua Linnert, Uwe Wolfrum
Summary: VLGR1/ADGRV1 is a large adhesion G protein-coupled receptor associated with Usher syndrome, epilepsy, and other diseases. It is expressed widely in the CNS, eye, and inner ear. Previous research has shown that VLGR1 plays a role in focal adhesion dynamics and cell migration. This study aimed to elucidate the mechanisms of VLGR1 in focal adhesion turnover.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Article
Pharmacology & Pharmacy
Joshua Linnert, Baran E. Gueler, Jacek Krzysko, Uwe Wolfrum
Summary: VLGR1/ADGRV1 is the largest known adhesion G protein-coupled receptor, and mutations in VLGR1/ADGRV1 are associated with Usher syndrome and epilepsy. This study identified autophagosomes as potential interacting proteins of VLGR1 and revealed the molecular and functional interaction between VLGR1 and key components of the autophagy process. These findings provide insights into the pathomechanisms underlying human USH and epilepsy related to VLGR1 defects.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Article
Cell Biology
Joshua Linnert, Barbara Knapp, Baran E. Gueler, Karsten Boldt, Marius Ueffing, Uwe Wolfrum
Summary: The human Usher syndrome is characterized by progressive vision and hearing loss. Mutations in ADGRV1 and CIB2 genes are associated with two sub-types of Usher syndrome. The proteins encoded by these two genes belong to distinct protein families. The cellular functions of ADGRV1 and CIB2 are still unclear, but they are found to interact with each other and play a role in primary cilia function.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Cell Biology
Jessica Schaefer, Nicole Wenck, Katharina Janik, Joshua Linnert, Katarina Stingl, Susanne Kohl, Kerstin Nagel-Wolfrum, Uwe Wolfrum
Summary: Human Usher syndrome (USH) is a complex genetic disorder that causes combined deafness and blindness. The underlying mechanisms of the disease, particularly in the eye and retina, are not well understood. This study identifies a role for the scaffold protein harmonin, encoded by the USH1C gene, in regulating the canonical Wnt/beta-catenin signaling pathway. The findings suggest that USH1C/harmonin acts as a suppressor of the pathway, and dysregulation of this pathway may contribute to the development of USH.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Biochemical Research Methods
Baran E. Gueler, Jacek Krzysko, Uwe Wolfrum
Summary: This protocol provides a fast and cost-effective technique for isolating, culturing, and maintaining primary mouse astrocytes at -80% purity levels, which can be used in in vitro studies for migration and focal adhesion dynamics. Additionally, an optimized transfection and manual quantification approach for focal adhesion analysis in fixed and living cells is presented.
Article
Neurosciences
Ryan P. Silk, Hanagh R. Winter, Ouria Dkhissi-Benyahya, Carmella Evans -Molina, Alan W. Stitt, Vijay K. Tiwari, David A. Simpson, Eleni Beli
Summary: This study investigates whether diabetes affects the daily rhythm of gene expression in the retina. The results show that diabetic mice exhibited phase advancement in the expression of certain genes compared to non-diabetic mice. The study also identified oxygen-sensing mechanisms and HIF1alpha as potential upstream regulators. These findings provide important insights into the development of diabetic retinopathy.
Article
Neurosciences
Krishnamachari S. Prahalad, Daniel R. Coates
Summary: Visual stimuli presented around the time of a saccade can be perceived differently by the visual system, including a reduction in the harmful impact of flankers. This study investigated the effects of microsaccades on crowded stimuli placed 20 arc minutes from the center of gaze. The findings suggest two separate pre-saccadic benefits, one that regularizes the crowding zone and another that specifically benefits microsaccade targets surrounded by tangential flankers.
Article
Neurosciences
Chandrika Ravisankar, Christopher W. Tyler, Clifton M. Schor, Shrikant R. Bharadwaj
Summary: This study revealed that less than one-third of adults with normal binocular vision were able to successfully free-fuse random-dot image pairs and identify the embedded stereoscopic shapes. The successful participants showed a dissociation of vergence and accommodative responses, while the unsuccessful ones either exhibited strong vergence and accommodation or weak vergence and strong accommodation. Task performance of the unsuccessful cluster improved significantly with pharmacological paralysis of accommodation. A minority of participants also learned to dissociate one direction of their vergence and accommodation crosslinks with repeated free-fusion trials, optimizing their task performance.