Article
Biochemistry & Molecular Biology
Mirjana Bjelos, Mladen Busic, Ana Curic, Borna Saric, Damir Bosnar, Leon Markovic, Biljana Kuzmanovic Elabjer, Benedict Rak
Summary: This case report presents a novel point mutation RPE65 c.353G>A, p.(Arg118Lys) associated with severe clinical presentation and complete macular atrophy in retinitis pigmentosa. The study suggests that this mutation should be reclassified as likely pathogenic due to its contribution to the pathological phenotype.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Young Hoon Jung, Jay Jiyong Kwak, Kwangsic Joo, Hyuk Jun Lee, Kyu Hyung Park, Min Seok Kim, Eun Kyoung Lee, Suk Ho Byeon, Christopher Seungkyu Lee, Jinu Han, Junwon Lee, Chang Ki Yoon, Se Joon Woo
Summary: This study investigated the clinical features, natural course, and genetic characteristics of Koreans with rhodopsin-associated retinitis pigmentosa (RHO-associated RP). The study found that the generalized RP group had a higher rate of visual field impairment progression to late-stage RP compared to the sector RP group. Best-corrected visual acuity deterioration was observed only in the generalized RP group. The study also identified several RHO gene mutations, including some that presented with both generalized and sector RP phenotypes.
FRONTIERS IN GENETICS
(2023)
Review
Biochemistry & Molecular Biology
Daiki Sakai, Hiroshi Tomita, Akiko Maeda
Summary: Optogenetics is a breakthrough in neuroscience with potential applications in treating retinal degenerative diseases. Clinical trials are currently underway to restore vision using optogenetic therapy. Choosing the right optogenetic tools and gene delivery methods is crucial for post-treatment vision improvement.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Laura Kuehlewein, Ditta Zobor, Katarina Stingl, Melanie Kempf, Fadi Nasser, Antje Bernd, Saskia Biskup, Frans P. M. Cremers, Muhammad Imran Khan, Pascale Mazzola, Karin Schaeferhoff, Tilman Heinrich, Tobias B. Haack, Bernd Wissinger, Eberhart Zrenner, Nicole Weisschuh, Susanne Kohl
Summary: This study investigated the phenotypic and genotypic features of retinitis pigmentosa associated with PDE6B gene variants, with most mutations being splicing defects and missense mutations. 43% of the PDE6B variants found in patients were novel, contributing to the mutation spectrum of PDE6B.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Kitako Tabata, Eriko Sugano, Akito Hatakeyama, Yoshito Watanabe, Tomoya Suzuki, Taku Ozaki, Tomokazu Fukuda, Hiroshi Tomita
Summary: The study demonstrated that retinal ganglion cells were photosensitive after the transduction of optogenetic genes and did not induce any phototoxicity following exposure to continuous light.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Zachary C. Elmore, L. Patrick Havlik, Daniel K. Oh, Leif Anderson, George Daaboul, Garth W. Devlin, Heather A. Vincent, Aravind Asokan
Summary: The membrane-associated accessory protein (MAAP) is identified as a novel viral egress factor that promotes the secretion of AAV serotypes. MAAP contains a cationic amphipathic domain critical for AAV secretion. Restoring MAAP expression can rescue the secretion defect in various AAV serotypes with mutated start sites.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Angela H. Kim, Pei-Kang Liu, Yin-Hsi Chang, Eugene Yu-Chuan Kang, Hung-Hsuan Wang, Nelson Chen, Yun-Ju Tseng, Go Hun Seo, Hane Lee, Laura Liu, An-Ning Chao, Kuan-Jen Chen, Yih-Shiou Hwang, Wei-Chi Wu, Chi-Chun Lai, Stephen H. Tsang, Meng-Chang Hsiao, Nan-Kai Wang
Summary: This study describes the clinical characteristics and genetic testing results of seven patients with CSNB in Taiwan, and discusses the significance of these findings for the molecular etiology and genotype-phenotype correlation of CSNB. Some novel variants identified in this study have not been described in previous research, but further study is needed to determine their clinical significance. The future of gene therapy for CSNB patients is also reviewed and discussed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
Ophthalmology
Laura Kuehlewein, Torsten Strasser, Gunnar Blumenstock, Katarina Stingl, M. Dominik Fischer, Barbara Wilhelm, Eberhart Zrenner, Bernd Wissinger, Susanne Kohl, Nicole Weisschuh, Ditta Zobor
Summary: This study describes the natural course of disease progression in patients with PDE6A-associated arRP, and establishes a detailed genotype-phenotype correlation. The severity of different disease-causing PDE6A mutations in humans with respect to central visual function was ranked, and the small annual decline rates in central retinal function may pose challenges in assessing treatment efficacy in interventional trials.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Nanda Boon, C. Henrique Alves, Aat A. Mulder, Charlotte A. Andriessen, Thilo M. Buck, Peter M. J. Quinn, Rogier M. Vos, Abraham J. Koster, Carolina R. Jost, Jan Wijnholds
Summary: Mutations in the Crb1 gene lead to retinal diseases in rats, causing characteristic retinal changes and decreased visual acuity. Subretinal injection of AAV5 and AAV9 predominantly infect RPE and photoreceptor cells in mutant rats, while intravitreal injection of ShH10(Y445F) mainly infects Muller glial cells. Gene therapy using AAV vectors did not improve retinal function in Crb1 mutant rats, indicating the need for earlier expression of recombinant hCRB proteins in Muller glial cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Multidisciplinary Sciences
Ammanie Abdul-Fatah, Leila Esmaeilisaraji, Crisel Mae Juan, Martin Holcik
Summary: This paper provides support for the creation of a mitochondrial disease patient registry in Canada through a systematic scoping review. It also fills a knowledge gap by providing a narrative synthesis of published literature on these registries.
Article
Genetics & Heredity
Maria Kaukonen, Inka-Tuulevi Pettinen, Kaisa Wickstrom, Meharji Arumilli, Jonas Donner, Ida-Julia Juhola, Saila Holopainen, Joni A. Turunen, Masahito Yoshihara, Juha Kere, Hannes Lohi
Summary: Retinitis pigmentosa (RP) is a blinding eye disease affecting nearly two million people worldwide. Dogs, such as Lapponian herders (LHs), are affected with similar illnesses like progressive retinal atrophy (PRA). A recent study identified a novel genetic variant in the IFT122 gene in affected LHs, suggesting a new genetic cause for retinal dystrophies in the breed. This finding provides a new spontaneous dog model to study the role of IFT122 in RP biology.
Article
Ophthalmology
Jacque L. Duncan, Peiyao Cheng, Maureen G. Maguire, Allison A. Ayala, David G. Birch, Janet K. Cheetham, Todd A. Durham, Abigail T. Fahim, Carel B. Hoyng, Hiroshi Ishikawa, Michel Michaelides, Mark E. Pennesi, Jose-Alain Sahel, Katarina Stingl, Christina Y. Weng
Summary: A prospective observational study was conducted on 102 patients with USH2A-related retinal degeneration over a period of two years. It was found that quantitative measures of static perimetry significantly declined during this time. The greatest changes were observed in the full field and peripheral vision, while the central vision showed the least change.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2023)
Review
Chemistry, Multidisciplinary
Scott M. Stagg, Craig Yoshioka, Omar Davulcu, Michael S. Chapman
Summary: Adeno-associated virus (AAV) is a leading delivery vector in gene therapy treatments. Understanding the structure and molecular interactions of AAV with human hosts is of great interest. Electron microscopic approaches have been used to visualize the virus and its complexes, leading to important findings and new insights.
Article
Ophthalmology
Ling Liu, Danrui Cai, Xin Huang, Yin Shen
Summary: This study documented a case of an older female with concomitant acquired monocular blindness and COVID-19, highlighting the potential for retinal complications and severe vision loss in COVID-19 patients. Physicians should be aware of the possibility of fundus abnormalities or sudden vision loss in coronavirus-infected patients.
CURRENT EYE RESEARCH
(2021)
Article
Multidisciplinary Sciences
Tomokazu Fukuda, Kai Furuya, Kouhei Takahashi, Ai Orimoto, Eriko Sugano, Hiroshi Tomita, Sayo Kashiwagi, Tohru Kiyono, Tsuyoshi Ishii
Summary: This study compared the biological characteristics and genome-wide expression profiles of immortalized human dermal papilla cells generated by different methods to determine the optimal immortalization method. The data would be valuable to scientists aiming to establish new immortalized cell lines.
Article
Biochemistry & Molecular Biology
Yusaku Chukai, Takeshi Iwamoto, Ken Itoh, Hiroshi Tomita, Taku Ozaki
Summary: The study revealed that mitochondrial calpain-5 is activated under low Ca2+ concentrations and in response to endoplasmic reticulum stress, indicating its therapeutic potential in diseases associated with ER stress.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)
Article
Multidisciplinary Sciences
Kai Furuya, Tao Wu, Ai Orimoto, Eriko Sugano, Hiroshi Tomita, Tohru Kiyono, Takahiro Kurose, Yoshihiro Takai, Tomokazu Fukuda
Summary: The study investigated the expression patterns of immortalized corneal epithelial cells with different genetic modifications, showing that SV40 immortalized cells had a distinct expression pattern from wild-type cells regardless of serum presence, while corneal epithelial cells with combinatorial expression had a pattern closer to that of wild-type cells.
Article
Biochemistry & Molecular Biology
Kitako Tabata, Eriko Sugano, Akito Hatakeyama, Yoshito Watanabe, Tomoya Suzuki, Taku Ozaki, Tomokazu Fukuda, Hiroshi Tomita
Summary: The study demonstrated that retinal ganglion cells were photosensitive after the transduction of optogenetic genes and did not induce any phototoxicity following exposure to continuous light.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biotechnology & Applied Microbiology
Izzah Munirah, Taku Ozaki, Aya Sekine, Motoko Morimoto, Mayu Sugawara, Haruka Takada, Eriko Sugano, Hiroshi Tomita, Tohru Kiyono, Tomokazu Fukuda
Summary: Dogs are considered as the first animals to establish close relationship with humans, exhibiting unique genetic evolution and diversity. Domestic dogs are used in safety tests of pharmacological products, emphasizing the importance of considering the welfare of experimental animals. In this study, immortalized domestic dog-derived fibroblasts were successfully established as a potential in vivo model system for evaluating pharmacological chemicals without the need for animal testing.
Article
Cell Biology
Haruka Takada, Tomisato Miura, So Fujibayashi, Naomi Sasaki, Kouhei Takahashi, Eriko Sugano, Hiroshi Tomita, Taku Ozaki, Tohru Kiyono, Mitsuaki A. Yoshida, Tomokazu Fukuda
Summary: Cell immortalization allows for infinite expansion, but may alter the nature of the original cells. This study found that immortalized cells often exhibit chromosome abnormalities, while introducing CDK4, cyclin D1, and TERT can better maintain the original chromosome condition.
IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
(2021)
Article
Cell & Tissue Engineering
Yoshito Watanabe, Eriko Sugano, Kitako Tabata, Akito Hatakeyama, Tetsuya Sakajiri, Tomokazu Fukuda, Taku Ozaki, Tomoya Suzuki, Tatsuki Sayama, Hiroshi Tomita
Summary: The research team has successfully increased the light sensitivity of optogenetic gene-mediated therapy by designing mutants, which were used to restore visual responses in rats with genetically degenerating photoreceptor cells. The results suggest that ex3mV1Co may be an effective method for restoring advanced visual function.
NPJ REGENERATIVE MEDICINE
(2021)
Article
Cell Biology
Takenori Oikawa, Tomokazu Fukuda, Tetsuro Yamashita, Hiroshi Tomita, Taku Ozaki
Summary: The study shows that Tat-mu CL has a protective effect, effectively inhibiting glutamate-induced cell death and preventing nuclear translocation of AIF and DNA fragmentation. Therefore, Tat-mu CL may be a potential gene therapy modality for neurodegenerative diseases.
IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
(2022)
Article
Biochemistry & Molecular Biology
Yuki Kikuchi, Eriko Sugano, Shiori Yuki, Kitako Tabata, Yuka Endo, Yuya Takita, Reina Onoguchi, Taku Ozaki, Tomokazu Fukuda, Yoshihiro Takai, Takahiro Kurose, Koichi Tanaka, Yoichi Honma, Eduardo Perez, Maxwell Stock, Jose R. Fernandez, Masanori Tamura, Michael Voronkov, Jeffry B. Stock, Hiroshi Tomita
Summary: SIG-1451 partially protects against light-induced photoreceptor degeneration by inhibiting inflammatory responses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Daiki Sakai, Hiroshi Tomita, Akiko Maeda
Summary: Optogenetics is a breakthrough in neuroscience with potential applications in treating retinal degenerative diseases. Clinical trials are currently underway to restore vision using optogenetic therapy. Choosing the right optogenetic tools and gene delivery methods is crucial for post-treatment vision improvement.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Himari Matsusaka, Tao Wu, Kai Furuya, Tomoe Yamada-Kato, Lanlan Bai, Hiroshi Tomita, Eriko Sugano, Taku Ozaki, Tohru Kiyono, Isao Okunishi, Tomokazu Fukuda
Summary: This study identified downstream target genes involved in testosterone signalling in DPCs through RNA-Seq analysis, providing important data for the discovery of molecular targets for prostate cancer and AGA.
Article
Biochemistry & Molecular Biology
Akito Hatakeyama, Eriko Sugano, Tatsuki Sayama, Yoshito Watanabe, Tomoya Suzuki, Kitako Tabata, Yuka Endo, Tetsuya Sakajiri, Tomokazu Fukuda, Taku Ozaki, Hiroshi Tomita
Summary: Channelrhodopsins have been used in gene therapy to restore vision in patients with retinitis pigmentosa. The channel kinetics of ComV1 variants with different amino acid residues at the 172nd position were investigated. The study found that the characteristics of the amino acid at this position affect the radius of the ion gate, thereby altering the photocurrent and channel kinetics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Yuya Takita, Eriko Sugano, Kazuya Kitabayashi, Kitako Tabata, Akito Saito, Takanori Yokoyama, Reina Onoguchi, Tomokazu Fukuda, Taku Ozaki, Lanlan Bai, Hiroshi Tomita
Summary: This study used multifocal electroretinography to evaluate focal retinal function in rats exposed to continuous light. The results showed a significant decrease in retinal function after 24 hours of light exposure, with a regional dependency in retinal damage.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Kai Furuya, So Fujibayashi, Tao Wu, Kouhei Takahashi, Shin Takase, Ai Orimoto, Eriko Sugano, Hiroshi Tomita, Sayo Kashiwagi, Tohru Kiyono, Tsuyoshi Ishii, Tomokazu Fukuda
Summary: Testosterone signaling affects the focal adhesion pathway by regulating AR gene expression, with caveolin-1 as a target of AR regulation. This study provides important data resources for the discovery of new therapeutic targets for testosterone-related diseases.
Article
Biochemistry & Molecular Biology
Tetsuya Sakajiri, Masatoshi Nakatsuji, Yoshiaki Teraoka, Kosuke Furuta, Katsuya Ikuta, Kotoe Shibusa, Eriko Sugano, Hiroshi Tomita, Takashi Inui, Takaki Yamamura
Summary: The study investigates the interaction mechanism between ceruloplasmin and transferrin mediated by zinc. The findings suggest that zinc may play a role in the transfer of iron between ceruloplasmin and transferrin.
