Review
Ophthalmology
Bharatendu Chandra, Moon Ley Tung, Ying Hsu, Todd Scheetz, Val C. Sheffield
Summary: The primary cilium is a specialized organelle in eukaryotes that plays an important role in cell signaling and transportation. Ciliopathies are a group of disorders caused by ciliary dysfunction or abnormal ciliogenesis, with multiorgan involvement. Understanding the genetics and clinical features of ciliopathies, such as Bardet-Biedl syndrome, is challenging but crucial for therapeutic development. This review discusses the structure and function of primary cilia, their role in retinal photoreceptors, and the progress made in understanding ciliopathies.
PROGRESS IN RETINAL AND EYE RESEARCH
(2022)
Article
Multidisciplinary Sciences
Rui-Kai Zhang, Wei-Yue Sun, Yan-Xia Liu, Emma Y. Zhang, Zhen-Chuan Fan
Summary: This study reveals the mechanism of signal protein export from cilia via the RABL2-ARL3 cascade-mediated outward BBSome transition zone diffusion pathway.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Yan-Xia Liu, Wen -Juan Li, Rui-Kai Zhang, Sheng-Nan Sun, Zhen-Chuan Fan
Summary: Certain ciliary signaling proteins are transported from the tip to the base of cilia via retrograde intraflagellar transport (IFT), facilitated by the BBSome and ARL13. The interaction between ARL13GTP and BBS3GTP at the ciliary tip plays a crucial role in properly coupling the BBSome with signaling cargo. This understanding provides mechanistic insights into the defects seen in hedgehog signaling in humans with ARL13b and BBS3 mutations.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Oksana Tsyklauri, Veronika Niederlova, Elizabeth Forsythe, Avishek Prasai, Ales Drobek, Petr Kasparek, Kathryn Sparks, Zdenek Trachtulec, Jan Prochazka, Radislav Sedlacek, Philip Beales, Martina Huranova, Ondrej Stepanek
Summary: Bardet-Biedl Syndrome (BBS) patients and corresponding mouse models show higher prevalence of autoimmune diseases and alterations in the hematopoietic system. Dysfunction of the BBSome complex, a common cause of BBS, regulates B cell development in mice and affects canonical WNT signaling. This study reveals a connection between ciliopathy and dysregulated immune and hematopoietic systems.
Article
Biochemistry & Molecular Biology
Emanuela Marchese, Marianna Caterino, Roberta Fedele, Francesca Pirozzi, Armando Cevenini, Neha Gupta, Diego Ingrosso, Alessandra Perna, Giovambattista Capasso, Margherita Ruoppolo, Miriam Zacchia
Summary: This study provides insights into the mechanisms underlying renal disease in Bardet-Biedl syndrome (BBS) through urine metabolomic and proteomic analyses. The increased urinary excretion of lactate suggests a possible renal-specific defective handling. The BBS10 gene may play a role in renal metabolism, RNA processing, and cell proliferation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
I Perea-Romero, F. Blanco-Kelly, I Sanchez-Navarro, I Lorda-Sanchez, S. Tahsin-Swafiri, A. Avila-Fernandez, I Martin-Merida, M. J. Trujillo-Tiebas, R. Lopez-Rodriguez, M. Rodriguez de Alba, I. F. Iancu, R. Romero, M. Quinodoz, H. Hakonarson, Blanca Garcia-Sandova, P. Minguez, M. Corton, C. Rivolta, C. Ayuso
Summary: The study aimed to improve clinical and molecular diagnosis of SRDs by applying structured phenotypic ontology and NGS-based pipelines. Ciliopathies were found to be the most common SRD type, with a global characterization rate of 52% and an improved rate of 83% for prospective cases. Some cases were reclassified into a different clinical category after identification of the disease-causing gene.
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
Genetics & Heredity
Arleta Waszczykowska, Krzysztof Jeziorny, Dobromila Baranska, Katarzyna Matera, Aleksandra Pyziak-Skupien, Michal Ciborowski, Agnieszka Zmyslowska
Summary: This study evaluated the indicators of nervous system changes in ALMS and BBS patients using OCT and MRS methods. The results showed lower macular thickness in the patient group and differences in metabolite levels in brain areas. These findings contribute to the understanding of the pathophysiology of these rare diseases and offer insights for new therapies.
Article
Cell Biology
Sara K. Mayer, Jacintha Thomas, Megan Helms, Aishwarya Kothapalli, Ioana Cherascu, Adisa Salesevic, Elliot Stalter, Kai Wang, Poppy Datta, Charles Searby, Seongjin Seo, Ying Hsu, Sajag Bhattarai, Val C. Sheffield, Arlene V. Drack
Summary: Bardet-Biedl syndrome (BBS) is a genetic disorder caused by mutations in multiple genes, leading to early-onset retinal degeneration. This study phenotyped Bbs10 mice and identified a progressive degeneration of the outer nuclear layer, providing endpoints for preclinical trials.
DISEASE MODELS & MECHANISMS
(2022)
Review
Nutrition & Dietetics
Avital Horwitz, Ruth Birk
Summary: Obesity is a metabolic state characterized by the expansion of adipose tissue, which is regulated by genetics and excess energy intake. While the genetic regulation of adipose tissue expansion is not fully understood, studies on both monogenic and syndromic obesity have identified several genes related to obesity. Syndromic obesity, such as Bardet-Biedl syndrome (BBS), involves additional features and provides insights into peripheral adipocyte regulation in obesity. This review summarizes current knowledge on adipocyte hyperplasia and hypertrophy in common obesity and highlights the importance of studying syndromic obesity models like BBS.
Article
Genetics & Heredity
Urszula Smyczynska, Marcin Stanczak, Miljan Kuljanin, Aneta Wlodarczyk, Ewelina Stoczynska-Fidelus, Joanna Taha, Bartlomiej Pawlik, Maciej Borowiec, Joseph D. D. Mancias, Wojciech Mlynarski, Piotr Rieske, Wojciech Fendler, Agnieszka Zmyslowska
Summary: This study conducted transcriptomic and proteomic analysis on cellular models of Alstrom syndrome and Bardet-Biedl syndrome, identifying common and distinct pathological mechanisms between the two syndromes. Genes related to lipid and glycosaminoglycan metabolism and small molecule transport were downregulated, while those associated with signal transduction, immune system, cell cycle control, and DNA replication and repair were upregulated. Protein pathways involved in autophagy, apoptosis, cilium assembly, and Gli1 protein were also upregulated in both syndromes.
Article
Genetics & Heredity
Aziz Belkadi, Gaurav Thareja, Adnan Khan, Nisha Stephan, Shaza Zaghlool, Anna Halama, Ayeda Abdulsalam Ahmed, Yasmin A. Mohamoud, Joel Malek, Karsten Suhre, Rayaz A. Malik
Summary: This study uses ophthalmic imaging to identify novel retinal and corneal abnormalities in patients with Bardet-Biedl syndrome, expanding the phenotype of this disease.
BMC MEDICAL GENOMICS
(2023)
Review
Cell Biology
Nan-Xi Zheng, Ya-Ting Miao, Xi Zhang, Mu-Zhi Huang, Muhammad Jahangir, Shilin Luo, Bing Lang
Summary: Cilium is a conserved antenna-like structure on mammalian cells, and dysfunctional primary cilia are associated with various congenital diseases. Intraflagellar transport (IFT) is essential for maintaining cilia function, and disrupted IFT contributes to ciliopathies. IFT172 is a newly identified protein related to rare ciliopathies such as MZSDS and BBS, and this review summarizes its genetic and protein characteristics and its role in intraflagellar transport.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Cell Biology
Toneisha Stubbs, James I. Bingman, Jason Besse, Kirk Mykytyn
Summary: Primary cilia are important for neuronal functions and their dysfunction is linked to ciliopathies. Bardet-Biedl syndrome proteins play a crucial role in trafficking G protein-coupled receptors (GPCRs) in neuronal cilia, and their absence leads to abnormal localization of signaling proteins in the brain.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Endocrinology & Metabolism
Deng-Fu Guo, Ronald A. Merrill, Lan Qian, Ying Hsu, Qihong Zhang, Zhihong Lin, Daniel R. Thedens, Yuriy M. Usachev, Isabella Grumbach, Val C. Sheffield, Stefan Strack, Kamal Rahmouni
Summary: The study reveals that the BBSome protein complex plays a critical role in regulating mitochondrial dynamics and function. The disruption of the BBSome leads to excessive fusion of mitochondria in various cell types, and this morphological change is associated with functional abnormalities, including reduced oxygen consumption rate and altered mitochondrial distribution and calcium handling. Mechanistically, the BBSome modulates the activity of the key regulator protein DRP1 through regulating its phosphorylation and translocation, and rescuing the decrease in DRP1 activity can normalize the defects induced by BBSome deficiency.
MOLECULAR METABOLISM
(2023)
Article
Pathology
Zhongxiao Wang, Chi-Hsiu Liu, Ye Sun, Yan Gong, Tara L. Favazza, Peyton C. Morss, Nicholas J. Saba, Thomas W. Fredrick, Xi He, James D. Akula, Jing Chen
AMERICAN JOURNAL OF PATHOLOGY
(2016)
Article
Ophthalmology
Naoyuki Tanimoto, James D. Akula, Anne B. Fulton, Bernhard H. F. Weber, Mathias W. Seeliger
DOCUMENTA OPHTHALMOLOGICA
(2016)
Article
Ophthalmology
Andrea Elizabeth Arriola-Lopez, M. Elena Martinez-Perez, Maria Ana Martinez-Castellanos
Article
Immunology
Ye Sun, Zhiqiang Lin, Chi-Hsiu Liu, Yan Gong, Raffael Liegl, Thomas W. Fredrick, Steven S. Meng, Samuel B. Burnim, Zhongxiao Wang, James D. Akula, William T. Pu, Jing Chen, Lois E. H. Smith
JOURNAL OF EXPERIMENTAL MEDICINE
(2017)
Article
Ophthalmology
Ronald M. Hansen, Anne Moskowitz, James D. Akula, Anne B. Fulton
PROGRESS IN RETINAL AND EYE RESEARCH
(2017)
Article
Endocrinology & Metabolism
Zhongjie Fu, Zhongxiao Wang, Chi-Hsiu Liu, Yan Gong, Bertan Cakir, Raffael Liegl, Ye Sun, Steven S. Meng, Samuel B. Burnim, Ivana Arellano, Elizabeth Moran, Rubi Duran, Alexander Poblete, Steve S. Cho, Saswata Talukdar, James D. Akula, Ann Hellstrom, Lois E. H. Smith
Article
Neurosciences
Zai-Long Chi, Avner Adini, Amy E. Birsner, Lauren Bazinet, James D. Akula, Robert J. D'Amato
Article
Multidisciplinary Sciences
M. Elena Martinez-Perez, Nicholas Witt, Kim H. Parker, Alun D. Hughes, Simon A. M. Thom
Article
Ophthalmology
James D. Akula, Lucia Ambrosio, Fiona I. Howard, Ronald M. Hansen, Anne B. Fulton
EXPERIMENTAL EYE RESEARCH
(2019)
Article
Multidisciplinary Sciences
M. Elena Martinez-Perez, Alun D. Hughes, Simon A. McG. Thom, Kim H. Parker, Nicholas W. Witt
Summary: This study explores the possibility of using low-cost handheld retinal imaging devices for automatically extracting quantifiable measures of retinal blood vessels. The optical properties of available handheld devices were compared using a Zeiss model eye with a USAF resolution test chart. The Horus DEC 200 was the only suitable camera, but it exhibited shortcomings in capturing images of human eyes compared to the Canon CR-DGi retinal desktop camera. Potential improvements are discussed to enhance the performance of handheld retinal imaging devices for quantitative retinal microvascular measurements.
ROYAL SOCIETY OPEN SCIENCE
(2023)
Article
Medicine, General & Internal
Mircea Mujat, James D. Akula, Anne B. Fulton, R. Daniel Ferguson, Nicusor Iftimia
Summary: Adaptive optics improves resolution in ophthalmic imaging for identifying, counting, and mapping retinal microstructures. Small patches can be registered using cross-correlation, but larger images require more sophisticated techniques. We have applied a non-rigid registration technique to compensate for local image deformations, resulting in improved definition of retinal microstructures. Evaluation of derived metrics can facilitate early diagnostics of retinal diseases.
Proceedings Paper
Optics
M. Elena Martinez-Perez, Kim H. Parker, Nick Witt, Alun D. Hughes, Simon A. M. Thom
TWELFTH INTERNATIONAL CONFERENCE ON MACHINE VISION (ICMV 2019)
(2020)
Article
Medicine, Research & Experimental
Zhongjie Fu, Chatarina A. Lofqvist, Raffael Liegl, Zhongxiao Wang, Ye Sun, Yan Gong, Chi-Hsiu Liu, Steven S. Meng, Samuel B. Burnim, Ivana Arellano, My T. Chouinard, Rubi Duran, Alexander Poblete, Steve S. Cho, James D. Akula, Michael Kinter, David Ley, Ingrid Hansen Pupp, Saswata Talukdar, Ann Hellstrom, Lois E. H. Smith
EMBO MOLECULAR MEDICINE
(2018)
Proceedings Paper
Computer Science, Artificial Intelligence
E. Hernandez-Sanchez, M. Elena Martinez-Perez, A. Gastelum-Strozzi
PROCEEDINGS OF 2016 FUTURE TECHNOLOGIES CONFERENCE (FTC)
(2016)
Article
Ophthalmology
Ramkumar Ramamirtham, James D. Akula, Garima Soni, Matthew J. Swanson, Jennifer N. Bush, Anne Moskowitz, Emily A. Swanson, Tara L. Favazza, Jena L. Tavormina, Mircea Mujat, R. Daniel Ferguson, Ronald M. Hansen, Anne B. Fulton
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2016)
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.
