Article
Chemistry, Multidisciplinary
Kim Nguyen, Yajun Wang, Whitney E. England, John C. Chaput, Robert C. Spitale
Summary: The study demonstrates the utility of XNAzyme X10-23 in targeting allele-specific mRNA sequences in cells, particularly for difficult-to-treat disease-causing mutations. Catalytic XNAs show potential for suppressing mRNA expression carrying disease-causing mutations that are challenging to target at the protein level with conventional small molecule therapeutics.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Cell Biology
Ashish K. Solanki, Manas R. Biswal, Stephen Walterhouse, Rene Martin, Altaf A. Kondkar, Hans-Joachim Knolker, Bushra Rahman, Ehtesham Arif, Shahid Husain, Sandra R. Montezuma, Deepak Nihalani, Glenn Prazere Lobo
Summary: The unconventional myosin MYO1C plays a crucial role in rhodopsin localization to photoreceptor outer segments and is essential for normal visual function. Loss of MYO1C in mice leads to rhodopsin mislocalization, impaired photoreceptor function, and progressively shorter outer segments, indicating its significance in retinal cell physiology.
Article
Ophthalmology
Alexander Kolesnikov, Jennings Luu, Hui Jin, Krzysztof Palczewski, Vladimir J. Kefalov
Summary: This study examined the effects of PP2A deficiency in the absence of GRK1 or Arr1 on rod photoreceptor viability. The results showed that while PP2A is not necessary for the survival of rods, its deletion accelerates the degeneration caused by the absence of either GRK1 or Arr1.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Ophthalmology
Shannon R. Barwick, Haiyan Xiao, David Wolff, Jing Wang, Elizabeth Perry, Brendan Marshall, Sylvia B. Smith
Summary: Retinitis pigmentosa (RP) is a devastating inherited retinal disease that leads to visual impairment and blindness. Currently, there is no cure for RP, highlighting the importance of research into prolonging vision. This study investigated the effects of Sigma 1 receptor (Sig1R) activation in a mouse model of RP and found that it can protect visual function and structure. These results provide a framework for further studies on Sig1R as a potential therapeutic target for retinal degenerative diseases.
EXPERIMENTAL EYE RESEARCH
(2023)
Review
Neurosciences
Fangyuan Zhen, Tongdan Zou, Ting Wang, Yongwei Zhou, Shuqian Dong, Houbin Zhang
Summary: Rhodopsin is a light-sensitive receptor that initiates the phototransduction cascade. Mutations in the rhodopsin-encoding gene are the leading cause of retinitis pigmentosa. The high allelic heterogeneity suggests complex pathogenic mechanisms related to protein misfolding and dysfunction.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Lars Tebbe, Maggie L. Mwoyosvi, Ryan Crane, Mustafa S. Makia, Mashal Kakakhel, Dominic Cosgrove, Muayyad R. Al-Ubaidi, Muna I. Naash
Summary: The c.2299delG mutation in usherin leads to hearing and vision loss. In a mouse model, mutant usherin expression causes retinitis pigmentosa and structural defects in the photoreceptor cilium with mislocalization of VLGR1 and WHRN. Usher syndrome (USH) is the leading cause of combined deafness-blindness, and a knock-in mouse expressing the c.2299delG mutation of usherin was generated to mimic the patient's retinal phenotype. This mouse model exhibits retinal degeneration, mislocalization of usherin interactors, and an earlier onset of symptoms compared to the knockout model.
NATURE COMMUNICATIONS
(2023)
Article
Neurosciences
Meng- Zhao, Houting Lv, Na Yang, Guang-Hua Peng
Summary: The study investigated the mechanism of retinal photoreceptor degeneration by establishing a stable retinitis pigmentosa (RP) model. It was found that activation of mTOR may be associated with RP, and the use of mTOR inhibitor rapamycin improved retinal function and photoreceptor thickness and morphology, possibly by activating autophagy to protect retinal photoreceptors.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Angela Armento, Aparna Murali, Julia Marzi, Ana C. Almansa-Garcia, Blanca Arango-Gonzalez, Ellen Kilger, Simon J. Clark, Katja Schenke-Layland, Charmaine A. Ramlogan-Steel, Jason C. Steel, Marius Ueffing
Summary: The study utilizing a co-culture model demonstrated the detrimental effects of FH loss in RPE cells on the retina, with observed changes in mitochondrial and lipid composition. The model is applicable not only to porcine retinal explants but also to human retinal explants, providing valuable insights for AMD research.
Article
Multidisciplinary Sciences
Hui Peng, Prerana Ramadurgum, DaNae R. Woodard, Steffi Daniel, Emi Nakahara, Marian Renwick, Bogale Aredo, Shyamtanu Datta, Bo Chen, Rafael Ufret-Vincenty, John D. Hulleman
Summary: The DHFR DD system can be effectively applied in various mouse models of ocular diseases, providing a foundation for the conditional control of gene therapy to treat multiple eye diseases.
Article
Biochemistry & Molecular Biology
Elena Marrocco, Rosa Maritato, Salvatore Botta, Marianna Esposito, Enrico Maria Surace
Summary: The synthetic transcriptional repressor ZF6-DB designed for treating retinitis pigmentosa does not disrupt murine retinal development while effectively blocking target gene expression. Delivery of ZF6-DB during retinal development in mice results in morphological and functional recovery of the retina in a model of retinitis pigmentosa. The study suggests the use of developmental transitions as a safe approach for retinal gene therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Ophthalmology
Dawiyat Massoudi, Sean Gorman, Yien-Ming Kuo, Takao Iwawaki, Scott A. Oakes, Feroz R. Papa, Douglas B. Gould
Summary: This study evaluated the contribution of IRE1a to photoreceptor development, homeostasis, and degeneration. The results suggest that IRE1a is dispensable for photoreceptor development but important for photoreceptor homeostasis in aging retinas and for protecting against ER stress-mediated photoreceptor degeneration.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2023)
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
Biochemistry & Molecular Biology
Katsuyuki Nagata, Daisuke Hishikawa, Hiroshi Sagara, Masamichi Saito, Sumiko Watanabe, Takao Shimizu, Hideo Shindou
Summary: Retinal photoreceptor cells require specialized lipid metabolism for their survival and function. The production of saturated phosphatidylcholine (PC) by LPCAT1 plays a critical role in photoreceptor maturation. This study found that genetic deletion of Lpcat1 causes light-independent and photoreceptor-specific apoptosis in mice, affecting membrane lipid composition and mitochondrial reactive oxygen species levels in photoreceptor cells.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Genetics & Heredity
Andreas R. Janecke, Xiaoqin Liu, Ruediger Adam, Sumanth Punuru, Arne Viestenz, Valeria Strauss, Martin Laass, Elizabeth Sanchez, Roberto Adachi, Martha P. Schatz, Ujwala S. Saboo, Naveen Mittal, Klaus Rohrschneider, Johanna Escher, Anuradha Ganesh, Sana Al Zuhaibi, Fathiya Al Murshedi, Badr AlSaleem, Majid Alfadhel, Siham Al Sinani, Fowzan S. Alkuraya, Lukas A. Huber, Thomas Mueller, Ruth Heidelberger, Roger Janz
Summary: New STX3 variants have been found to be associated with a syndrome including congenital enteropathy and retinal dystrophy. These variants affect STX3 transcripts, leading to reduced numbers of photoreceptors and thinning of cell layers.
Article
Cell Biology
Fahad Farhan, Mohammad Almarhoun, Aileen Wong, Amy S. Findlay, Chris Bartholomew, Mark T. S. Williams, Toby W. Hurd, Xinhua Shu
Summary: TSPO knockout mice exhibited elevated cholesterol levels, disrupted cholesterol efflux, downregulation of cholesterol-associated genes, increased production of pro-inflammatory cytokines, and microglial activation in the retina, providing insights for potential therapeutic strategies for age-related macular degeneration (AMD).