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
Chemistry, Medicinal
Eliav Blum, Jianye Zhang, Jordan Zaluski, David E. Einstein, Edward E. Korshin, Adam Kubas, Arie Gruzman, Gregory P. Tochtrop, Philip D. Kiser, Krzysztof Palczewski
Summary: The recycling of all-trans-retinal to 11-cis-retinal through the visual cycle is essential in the eye's metabolic pathway. A new series of emixustat derivatives with strategically placed fluorine and deuterium atoms have been designed to slow down key metabolic transformations of emixustat. Crystal structures and quantum chemical analysis revealed how fluoro substituents can be accommodated within the active site pocket of RPE65.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Ophthalmology
Philip D. Kiser
Summary: This article reviews the importance of RPE65 in the visual cycle and the recent advances made in this field. It discusses the catalytic mechanism of RPE65, its phylogenetic origins, the relationship between its membrane binding affinity and catalytic activity, and its role in visual chromophore production, among other topics. Furthermore, it highlights key questions for future research pursuits.
PROGRESS IN RETINAL AND EYE RESEARCH
(2022)
Article
Ophthalmology
Nicholas P. Boyer, Debra A. Thompson, Yiannis Koutalos
Summary: The study investigated the contribution of all-trans retinal to the formation and stability of RPE lipofuscin in Rdh8(-/-) mice reared under cyclic-light conditions. Results showed that the levels of A2E and RPE lipofuscin accumulated faster in cyclic-light-reared mice compared to dark-reared mice, but the impact of increased all-trans retinal was modest. Additionally, moving cyclic-light-reared mice to darkness led to unexpected decreases in A2E levels, suggesting a potential therapeutic target for controlling A2E cytotoxicity.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Article
Cell Biology
Miwa Hara, Hara Wenjing, Volha V. Malechka, Yusuke Takahashi, Jian-Xing Ma, Gennadiy Moiseyev
Summary: PNPLA2 acts as a phospholipase in the endoplasmic reticulum, mobilizing retinyl esters from retinosomes and playing a crucial role in the visual cycle.
Article
Cell Biology
Joe M. Butler, Wasu Supharattanasitthi, Yit C. Yang, Luminita Paraoan
Summary: The study reveals that with age, there is an increase in transcription of main RPE-associated visual cycle genes in human RPE, showing a positive correlation with the accumulation of retinoid by-products and involvement of retinoic acid receptor alpha transcription factor.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2021)
Article
Cell Biology
Aleksander Tworak, Alexander Kolesnikov, John D. Hong, Elliot H. Choi, Jennings C. Luu, Grazyna Palczewska, Zhiqian Dong, Dominik Lewandowski, Matthew J. Brooks, Laura Campello, Anand Swaroop, Philip D. Kiser, Vladimir J. Kefalov, Krzysztof Palczewski
Summary: Using a cell-specific gene reactivation approach, we investigated the kinetics of RGR-mediated recovery of photoreceptor responses. We found that both RPE and a specialized subset of Mueuroller glia contribute to scotopic and photopic function, and demonstrated the role of 11-cis-retinal in rapid visual pigment regeneration.
Article
Medicine, General & Internal
Hung-Da Chou, Yih-Shiou Hwang, Kuan-Jen Chen, Wei-Chi Wu, Laura Liu, Shyh-Tyan Ou, Webber Liao, Cheng-Chi Wang, Tom Lin, Chi-Chun Lai
Summary: This study found that age-related macular degeneration (AMD) associated with ABCA4 variants is characterized by the accumulation of visual cycle-byproduct lipofuscin. Reducing retinol-binding protein 4 (RBP4) may reduce lipofuscin production. The study also found that higher levels of RBP4 are associated with the severity of AMD.
Article
Chemistry, Physical
Abhigyan Sengupta, Lorenz E. Rognoni, Ulrich Merkel, Gabriel Zoldak, Matthias Rief
Summary: Prolyl isomerization catalyzed by the PPIase enzyme plays a crucial role in cellular signaling and molecular timing. This study demonstrates a 25-fold acceleration of trans-cis isomerization rate and a stabilization effect on the cis-isomer by SlyD in a single-molecule experiment with FlnA20 protein.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Article
Multidisciplinary Sciences
Mangaljeet Singh, Kirandeep Kaur, Avinash Sharma, Rajvir Kaur, Dimple Joshi, Megha Chatterjee, Iman Dandapath, Amarjeet Kaur, Harpreet Singh, Prabhjeet Singh
Summary: Peptidyl-prolyl cis-trans isomerases (PPIases) are enzymes capable of cis-trans isomerization of the prolyl peptide bond, playing essential roles in various cellular processes. This study conducted a genome-wide analysis of PPIases in different Penicillium spp. and found variations in gene numbers and activities under salt stress. The halotolerant strain P. oxalicum showed significant enhancement in mycelial PPIase activity under salt stress, suggesting the importance of these enzymes in salt stress adaptation.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Amal Sam Sunny, Vaidhyanathan Ramamurthy
Summary: The low-temperature matrix isolation method is commonly used to generate and store reactive molecules and characterize them through in situ IR spectroscopy. This study demonstrates that confined space can shift the equilibrium toward higher energy isomers as an alternative to temperature. Additionally, the ability to assemble characterizable organic aggregates in water highlights the value of water as a reaction medium, which is an area yet to be fully explored by photochemists.
PHOTOCHEMISTRY AND PHOTOBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jacqueline Plau, Christopher E. Morgan, Yuriy Fedorov, Surajit Banerjee, Drew J. Adams, William S. Blaner, Edward W. Yu, Marcin Golczak
Summary: The dysregulation of retinoid metabolism is associated with prevalent ocular diseases, and modulating retinoid metabolism shows promise for their treatment. This study identified new chemical scaffolds for inhibitors of cellular retinol-binding protein 1 (CRBP1) through high-throughput screening. The researchers elucidated the interaction mechanism between CRBP1 and these inhibitors and provided a framework for the rational design of improved inhibitors for this class of lipid-binding proteins using protein crystallography, hydrogen/deuterium exchange mass spectrometry, and molecular dynamic simulations.
ACS CHEMICAL BIOLOGY
(2023)
Article
Ophthalmology
Lucas Janeschitz-Kriegl, Marco Cattaneo, Hendrik P. N. Scholl
Summary: The aim of this study was to investigate the concentration of RBP4 in different age groups of healthy individuals and check for abnormal levels in patients with STGD1 or GA. The results showed that age did not significantly impact RBP4 and SR levels in healthy individuals, and RBP4 and SR remained within normal limits in patients with STGD1 and GA.
OPHTHALMIC RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Hye Jin Kim, Jin Zhao, Jose L. Walewski, Janet R. Sparrow
Summary: High fat intake affects the functioning of photoreceptor cells by increasing the levels of bisretinoid and retinol-binding protein 4. This is likely due to the increased intake of vitamin A caused by a high fat diet.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
R. Krishnan Kutty, William Samuel, Todd Duncan, Olga Postnikova, Cynthia Jaworski, Chandrasekharam N. Nagineni, T. Michael Redmond
Article
Genetics & Heredity
Yan Li, Rachel Furhang, Amanda Ray, Todd Duncan, Joseph Soucy, Rashid Mahdi, Vijender Chaitankar, Linn Gieser, Eugenia Poliakov, Haohua Qian, Pinghu Liu, Lijin Dong, Igor B. Rogozin, T. Michael Redmond
Article
Multidisciplinary Sciences
Tamara L. Lenis, Jane Hu, Sze Yin Ng, Zhichun Jiang, Shanta Sarfare, Marcia B. Lloyd, Nicholas J. Esposito, William Samuel, Cynthia Jaworski, Dean Bok, Silvia C. Finnemann, Monte J. Radeke, T. Michael Redmond, Gabriel H. Travis, Roxana A. Radu
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2018)
Article
Genetics & Heredity
Olga A. Postnikova, Igor B. Rogozin, William Samuel, German Nudelman, Vladimir N. Babenko, Eugenia Poliakov, T. Michael Redmond
Article
Genetics & Heredity
Olga Postnikova, Eugenia Poliakov, Nady Golestaneh, Igor B. Rogozin, T. Michael Redmond
FRONTIERS IN GENETICS
(2019)
Article
Ophthalmology
Unikora Yang, Susan Gentleman, Xiaowu Gai, Michael B. Gorin, Mark S. Borchert, Thomas C. Lee, Adda Villanueva, Robert Koenekoop, Albert M. Maguire, Jean Bennett, T. Michael Redmond, Aaron Nagiel
JAMA OPHTHALMOLOGY
(2019)
Review
Biochemistry & Molecular Biology
Eugenia Poliakov, Sheetal Uppal, Igor B. Rogozin, Susan Gentleman, T. Michael Redmond
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2020)
Article
Biochemistry & Molecular Biology
Sheetal Uppal, Igor B. Rogozin, T. Michael Redmond, Eugenia Poliakov
Article
Biochemistry & Molecular Biology
Sheetal Uppal, Sergey A. Dergunov, Weiyu Zhang, Susan Gentleman, T. Michael Redmond, Eugene Pinkhassik, Eugenia Poliakov
Summary: Research has shown the important role of xanthophylls in human vision and their potential impact on antioxidant response. They offer benefits for preventing age-related macular degeneration and alleviating Alzheimer's disease symptoms.
Article
Biochemistry & Molecular Biology
Olga A. Postnikova, Sheetal Uppal, Weiliang Huang, Maureen A. Kane, Rafael Villasmil, Igor B. Rogozin, Eugenia Poliakov, T. Michael Redmond
Summary: The SARS-CoV-2 Spike glycoprotein has acquired a unique insert sequence that could affect virus spread and infection mechanisms, prompting further investigation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Saumil Sethna, Patrick A. Scott, Arnaud P. J. Giese, Todd Duncan, Xiaoying Jian, Sheikh Riazuddin, Paul A. Randazzo, T. Michael Redmond, Steven L. Bernstein, Saima Riazuddin, Zubair M. Ahmed
Summary: The research demonstrates the role of CIB2 in regulating the Rheb-mTORC1 signaling axis and autophagy in AMD. Molecular deficits and pathologies related to AMD were observed in Cib2 mutant mice and dry-AMD patient samples.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Saumil Sethna, Wadih M. Zein, Sehar Riaz, Arnaud Pj Giese, Julie M. Schultz, Todd Duncan, Robert B. Hufnagel, Carmen C. Brewer, Andrew J. Griffith, T. Michael Redmond, Saima Riazuddin, Thomas B. Friedman, Zubair M. Ahmed
Summary: Usher syndrome type I is a rare genetic disorder characterized by deafness, vestibular areflexia, and progressive retinal degeneration. A specific gene variant is prevalent in Ashkenazi Jews and accounts for a majority of USH1 cases. Studies in mouse models have shown similar visual deficits, suggesting potential therapeutic targets for preserving vision in USH1F patients.
Article
Multidisciplinary Sciences
Samuel William, Todd Duncan, T. Michael Redmond
Summary: This study demonstrates that pretreatment of ARPE-19 cells with sterculic acid, an inhibitor of the enzyme SCD, can prevent fenretinide-induced apoptosis. Sterculic acid shows antioxidant and anti-inflammatory effects, making it a potential therapeutic agent.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Sheetal Uppal, Olga Postnikova, Rafael Villasmil, Igor B. Rogozin, Alexander V. Bocharov, Thomas L. Eggerman, Eugenia Poliakov, T. Michael Redmond
Summary: Here, we provide evidence that LDLR plays a key role in the caveolae-mediated endocytosis pathway for SARS-CoV-2 virus internalization in ARPE-19 cells. Blocking ACE2 or cholesterol-rich lipid raft proteins did not prevent infection, while inhibition of cholesterol homeostasis using cyclodextrins and 25-HC reduced pseudovirion infection. Clathrin-dependent and flotillin-dependent rafts were not involved, but dynamin and caveolin-1 were found to be essential for virus entry. Furthermore, LDLR antibodies and siRNA-mediated knockdown of LDLR decreased pseudovirion infection. Therefore, we conclude that SARS-CoV-2 virus internalization in ARPE-19 cells primarily involves LDLR through a dynamin-dependent process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Sheetal Uppal, Tingting Liu, Eugenia Poliakov, Susan Gentleman, T. Michael Redmond
SCIENTIFIC REPORTS
(2019)