Article
Biochemistry & Molecular Biology
Enzo M. Vingolo, Lorenzo Casillo, Laura Contento, Francesca Toja, Antonio Florido
Summary: The study aimed to evaluate the relationship between circulating free radicals in blood and cystoid macular edema (CME) in Retinitis Pigmentosa (RP) patients. The results showed a significant increase in free oxygen radicals levels in RP patients with CME, suggesting that oxidative stress may accelerate cone cell damage.
Article
Biochemistry & Molecular Biology
Yogita Kanan, Sean F. Hackett, Henry T. Hsueh, Mahmood Khan, Laura M. Ensign, Peter A. Campochiaro
Summary: Retinitis pigmentosa (RP) is a genetic disorder that causes rod photoreceptor degeneration and subsequent cone photoreceptor degeneration. Reduced oxygen consumption from the loss of rods leads to retinal hyperoxia and oxidative stress, resulting in cone cell death and degeneration. However, reducing inspired oxygen levels can reduce retinal hyperoxia, preserve cone structure and function, and decrease oxidative damage in animal models of RP.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Lorena Olivares-Gonzalez, Sheyla Velasco, Idoia Gallego, Marina Esteban-Medina, Gustavo Puras, Carlos Loucera, Alicia Martinez-Romero, Maria Pena-Chilet, Jose Luis Pedraz, Regina Rodrigo
Summary: This study evaluated the effect of an essential fatty acid (EFA) supplement containing specialized pro-resolving mediators (SPMs) on retinal degeneration and microglia activation in a mouse model of RP. The EFA supplement improved retinal function, reduced inflammation and microglia activation, and reduced oxidative stress markers. These findings suggest that oral supplementation with SPMs such as the EFA supplement could be a potential therapeutic approach for resolving inflammation in RP.
Article
Nutrition & Dietetics
Lorena Olivares-Gonzalez, David Salom, Emilio Gonzalez-Garcia, David Hervas, Natalia Mejia-Chiqui, Mar Melero, Sheyla Velasco, Bianca Tabita Muresan, Isabel Campillo, Nieves Vila-Clerigues, Eduardo Lopez-Briz, Juan Francisco Merino-Torres, Jose Maria Millan, Jose Miguel Soriano Del Castillo, Regina Rodrigo
Summary: This study evaluated the effect of a 2-year nutritional intervention with antioxidant nutraceuticals on retinitis pigmentosa (RP) patients. The findings showed that the intervention improved retinal responses and reduced ocular oxidative damage, suggesting that long-term nutraceutical supplementation can slow down visual impairment and ameliorate ocular oxidative stress in RP.
FRONTIERS IN NUTRITION
(2022)
Article
Biochemistry & Molecular Biology
Javier Martinez-Gonzalez, Angel Fernandez-Carbonell, Antolin Canto, Roberto Gimeno-Hernandez, Inmaculada Almansa, Francisco Bosch-Morell, Maria Miranda, Teresa Olivar
Summary: This study demonstrates alterations in microglia and macroautophagy in an RP mouse model during the early stages of the disease. It suggests that inflammation and macroautophagy processes could be potential treatment alternatives for RP, while chaperone-mediated autophagy could be a therapeutic target in later stages. These findings provide important insights into the pathogenesis of RP and the development of treatment strategies.
Article
Biochemistry & Molecular Biology
Rocio Garcia-Arroyo, Aleix Gavalda-Navarro, Francesc Villarroya, Gemma Marfany, Serena Mirra
Summary: CERKL, a causative gene for Retinitis Pigmentosa, is involved in regulating autophagy, stress granules, and mitochondrial metabolism. Depletion of CERKL increases vulnerability of RPE mitochondria, leading to altered mitochondrial shape and respiratory dysfunction under oxidative stress conditions. Overexpression of CERKL protects the mitochondrial network against oxidative stress, suggesting its resilience in regulating mitochondrial function in RPE cells.
Article
Medicine, Research & Experimental
Yijing Yang, Ying Wang, Ying Deng, Jing Lu, Li Xiao, Jie Li, Yasha Zhou, Fujiao Nie, Xiangdong Chen, Jun Peng, Hanyu Tan, Yuhui Qin, Qinghua Peng
Summary: This study assessed the impact of Fructus Lycii and Salvia miltiorrhiza Bunge extract (FSE) on retinitis pigmentosa (RP) and explored the mechanism by which FSE can prevent oxidative stress-induced photoreceptor ferroptosis in RP via the P53/SLC7A11 pathway.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
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
Carla Enrica Gallenga, Maria Lonardi, Sofia Pacetti, Sara Silvia Violanti, Paolo Tassinari, Francesco Di Virgilio, Mauro Tognon, Paolo Perri
Summary: Retinitis pigmentosa is a genetic retinopathy, but non-genetic factors such as inflammation, autophagy, and oxidative stress play a crucial role in its pathogenesis and progression. Oxidative stress, caused by constant exposure to light/oxidative stress, results in accumulation of ROS in the retina, leading to microglial activation and photoreceptor degeneration. Various genetic mutations and alterations in cellular response contribute to the vicious cycle of neuroinflammation and degeneration in RP, suggesting microglia as a key target for oxidative stress therapy.
Article
Biochemistry & Molecular Biology
Lorena Fuentes-Broto, Lorena Perdices, Francisco Segura, Elvira Orduna-Hospital, Gema Insa-Sanchez, Ana Sanchez-Cano, Nicolas Cuenca, Isabel Pinilla
Summary: Retinitis pigmentosa (RP) is characterized by progressive loss of visual function, primarily affecting photoreceptors. Melatonin treatment showed beneficial effects on visual function, circadian rhythm, and oxidative stress in RP animal models and wild-type rats, suggesting its potential therapeutic value in age-related visual damage.
Article
Neurosciences
Yanli Ji, Meng Zhao, Xiaomeng Qiao, Guang-Hua Peng
Summary: This study explored the relationship between DNA methylation and photoreceptor cell death in retinitis pigmentosa. It was found that the overexpression of DNA methylation regulator DNMT3A/3B was associated with the damage of photoreceptor cells caused by MMS. The application of DNMT inhibitor 5-aza-dC partially restored the damage caused by MMS. These findings provide new evidence for DNMTs as potential therapeutic targets in retinal degenerative diseases.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Neurosciences
Ilaria Piano, Francesca Corsi, Beatrice Polini, Claudia Gargini
Summary: Treatment with naringenin and quercetin can alleviate retinal degeneration by preserving photoreceptor functionality and increasing antioxidant and anti-apoptotic pathways.
FRONTIERS IN NEUROSCIENCE
(2022)
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
Cell & Tissue Engineering
Eric D. Jong, Sabiha Hacibekiroglu, Lily Guo, Evan Sawula, Biao Li, Chengjin Li, Margaret T. Ho, Molly S. Shoichet, Valerie A. Wallace, Andras Nagy
Summary: A combined cell and gene therapy was developed for the treatment of retinitis pigmentosa (RP). Human embryonic stem cells (hESCs) were genetically engineered to differentiate into retinal pigment epithelium (hRPE) cells, which were used to protect and preserve photoreceptor cells in mouse models. This study reveals the potential of this therapy for RP treatment and the possibility of using hRPE cells for long-term delivery of therapeutic biologics.
STEM CELL RESEARCH & THERAPY
(2023)
Article
Plant Sciences
Chen Ou, Pengfei Jiang, Ye Tian, Zhen Yao, Yijing Yang, Jun Peng, Meiyan Zeng, Houpan Song, Qinghua Peng
Summary: The study demonstrated that the combination of Fructus Lycii and Salvia miltiorrhiza Bunge extract has protective effects on retinitis pigmentosa, potentially through regulating the Nrf2/HO-1 pathway to inhibit oxidative stress.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Article
Oncology
Yi Hu, Chun Yang, Tania Amorim, Mohsin Maqbool, Jenny Lin, Chen Li, Chuanfeng Fang, Li Xue, Ariel Kwart, Hua Fang, Mei Yin, Allison J. Janocha, Daisuke Tsuchimoto, Yusaku Nakabeppu, Xiaofeng Jiang, Alex Mejia-Garcia, Faiz Anwer, Jack Khouri, Xin Qi, Qing Y. Zheng, Jennifer S. Yu, Shan Yan, Thomas LaFramboise, Kenneth C. Anderson, Leal C. Herlitz, Nikhil C. Munshi, Jianhong Lin, Jianjun Zhao
Summary: This study identified APE2 as a critical molecule upregulated in the kidney following cisplatin treatment, leading to MYH9 dysfunction in mitochondria and potential development of AKI. Knockout of APE2 attenuated cisplatin-induced kidney injury, suggesting a novel target for prophylactic treatment of AKI.
Article
Multidisciplinary Sciences
Hiroki Sakamoto, Koji Miyanishi, Shingo Tanaka, Ryo Ito, Kota Hamaguchi, Akira Sakurada, Masanori Sato, Tomohiro Kubo, Takahiro Osuga, Kazuyuki Murase, Kohichi Takada, Yusaku Nakabeppu, Masayoshi Kobune, Junji Kato
Summary: The study found that MUTYH deficiency is associated with the development of liver tumors in NASH-related conditions. In mouse experiments, MUTYH-null mice fed a high-fat high-cholesterol+high-iron diet were more likely to develop liver tumors and showed higher accumulation of oxidative stress markers. Gene expression analysis also indicated involvement of the Wnt/beta-catenin signaling pathway and increased c-Myc expression in MUTYH-null liver tissues.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Sugako Oka, Julio Leon, Kunihiko Sakumi, Nona Abolhassani, Zijing Sheng, Daisuke Tsuchimoto, Frank M. LaFerla, Yusaku Nakabeppu
Summary: 8-Oxoguanine accumulates in Alzheimer's disease brains, and deficiency of MTH1 and OGG1 can increase its accumulation, leading to microglial activation and neuronal loss. Minocycline can inhibit microglial activation and reduce neuroinflammation, providing a potential new approach for preventing and treating AD.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Guianfranco Mazzei, Ryohei Ikegami, Nona Abolhassani, Naoki Haruyama, Kunihiko Sakumi, Takashi Saito, Takaomi C. Saido, Yusaku Nakabeppu
Summary: The study found that high-fat diet caused cognitive impairment, increased A beta deposition, and microgliosis in transgenic mouse models of Alzheimer's disease, accompanied by insulin resistance in the hippocampus.
Article
Biochemistry & Molecular Biology
Jingwen Chen, Xin Wu, Yanyi Wang, Yunfeng Pan, Yan Ren, Yusaku Nakabeppu, Yimei Fan, Yaping Wang
Summary: This study demonstrates that Mutyh deficiency can lead to changes in mitochondrial structure and impair mitochondrial function through downregulation of Mfn2 and alteration of the ratio of L-Opa1/S-Opa1, accompanied by a reduction in alpha-ketoglutaric acid (alpha-KG). Further analysis reveals that Mutyh deficiency may cause downregulation of histone demethylases and DNA demethylases and inhibition of Mfn2 transcription. Interestingly, supplementation of alpha-KG can alleviate the damage associated with Mutyh deficiency, restore Mfn2 expression, and prevent degradation of L-Opa1.
FREE RADICAL RESEARCH
(2022)
Article
Neurosciences
Yuri Mizuno, Nona Abolhassani, Guianfranco Mazzei, Takashi Saito, Takaomi C. Saido, Ryo Yamasaki, Jun-ichi Kira, Yusaku Nakabeppu
Summary: Oxidative stress is a major risk factor for Alzheimer's disease, characterized by the accumulation of 8-oxoG in the brain. Deficiency of MTH1 and OGG1 accelerates the accumulation of 8-oxoG in DNA and leads to reduced anxiety-related behavior in 6-month-old mice.
NEUROSCIENCE RESEARCH
(2022)
Article
Cell Biology
Chukwuemeka George Anene-Nzelu, Peter Yiqing Li, Tuan Danh Anh Luu, Shi Ling Ng, Zenia Tiang, Bangfen Pan, Wilson Lek Wen Tan, Matthew Ackers-Johnson, Ching Kit Chen, Yee Phong Lim, Rina Wang Miao Qin, Wee Woon Chua, Lim Xin Yi, Roger Sik-Yin Foo, Yusaku Nakabeppu
Summary: Doxorubicin, commonly used for cancer treatment, can cause cardiotoxicity. This study demonstrates that deficiency of OGG1 gene exacerbates doxorubicin-induced cardiac dysfunction and increases mortality in mice. Transcriptomic analysis reveals dysregulation of genes related to inflammation in the hearts of Ogg1 knockout mice.
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2022)
Article
Psychiatry
Kazuya Matsuo, Yasuharu Shinoda, Nona Abolhassani, Yusaku Nakabeppu, Kohji Fukunaga
Summary: This study explored molecular alterations in the hippocampus of rats with autism spectrum disorder (ASD) and the effects of chronic administration of intranasal oxytocin (OXT). The results revealed that prenatal valproic acid (VPA) exposure altered gene expression in the hippocampus, with some of these genes suggested as candidates for ASD and involved in memory, developmental processes, and epilepsy. OXT treatment partly improved the expression of these genes, which interacted with genes involved in social behaviors and hippocampal-dependent memory.
FRONTIERS IN PSYCHIATRY
(2022)
Article
Ophthalmology
Chihiro Murata, Yusuke Murakami, Takuma Fukui, Sakurako Shimokawa, Koh-Hei Sonoda, Kimihiko Fujisawa
Summary: This paper reported on 3 consecutive cases of MEKi-associated retinopathy with characteristic multiple SRDs, showing rapid resolution with cessation of MEKi treatment but quick recurrence after resumption. EOG tests revealed a marked decrease in LP:DT ratio in eyes with multiple SRDs.
CASE REPORTS IN OPHTHALMOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Teruya Nakamura, Yukari Koga-Ogawa, Kana Fujimiya, Mami Chirifu, Masataka Goto, Shinji Ikemizu, Yusaku Nakabeppu, Yuriko Yamagata
Summary: The human MTH1 protein recognizes substrates through the exchange of protonation states, and the protonation state change is related to its substrate binding ability.
Article
Neurosciences
Sayaka Okuzono, Fumihiko Fujii, Yuki Matsushita, Daiki Setoyama, Yohei Shinmyo, Ryoji Taira, Kousuke Yonemoto, Satoshi Akamine, Yoshitomo Motomura, Masafumi Sanefuji, Takeshi Sakurai, Hiroshi Kawasaki, Kihoon Han, Takahiro A. Kato, Hiroyuki Torisu, Dongchon Kang, Yusaku Nakabeppu, Yasunari Sakai, Shouichi Ohga
Summary: Epileptic seizures are common comorbidities in children with autism spectrum disorder (ASD), but little is known about the genes involved and their role in regulating neuronal excitability. This study found that Shank3, an ASD-associated gene, plays a unique role in protecting thalamocortical neurons from hyperexcitability during the early postnatal period. These findings have important implications for understanding the mechanisms underlying seizures in children with autism.
NEUROSCIENCE RESEARCH
(2023)
Article
Multidisciplinary Sciences
Yuya Fujii, Mitsuru Arima, Yusuke Murakami, Koh-Hei Sonoda
Summary: We successfully generated photoreceptor cells in mouse models of retinal degeneration through intravitreal injection of small molecule compounds alone. The optimal combination of compounds selected through in vitro screening was injected into the vitreous, leading to a significant increase in the number of rod cells and the expression of rhodopsin. Lineage tracing demonstrated that the rhodopsin-positive cells originated from endogenous Muller cells, accompanied by the recovery of rhodopsin-derived scotopic function.
Article
Biochemistry & Molecular Biology
Xu Zheng, Wenhe Zhang, Yinchao Hu, Zhexuan Zhao, Jiaxin Wu, Xiaoqing Zhang, Fengqi Hao, Jinling Han, Jing Xu, Wenjing Hao, Ruoxi Wang, Meihong Tian, Zsolt Radak, Yusaku Nakabeppu, Istvan Boldogh, Xueqing Ba
Summary: Exercise-induced generation of 8-oxoG promotes muscle remodeling and adaptation by activating the Ras-MEK-MyoD signal pathway. This study reveals the signaling role of DNA repair metabolite 8-oxoG in muscle remodeling and adaptation, and suggests its potential therapeutic application in muscle damage-related disorders.
Article
Ophthalmology
Shun Nakamura, Kohta Fujiwara, Noriko Yoshida, Yusuke Murakami, Shotaro Shimokawa, Yoshito Koyanagi, Yasuhiro Ikeda, Koh-Hei Sonoda
Summary: This study investigated the long-term outcomes of cataract surgery in patients with retinitis pigmentosa (RP). Many patients experienced vision loss after the surgery. The preoperative finding of preserved foveal ellipsoid zone (EZ) was associated with a better visual prognosis.
OPHTHALMOLOGY RETINA
(2022)
Article
Multidisciplinary Sciences
Jun Funatsu, Yusuke Murakami, Shotaro Shimokawa, Shunji Nakatake, Kohta Fujiwara, Ayako Okita, Masatoshi Fukushima, Kensuke Shibata, Noriko Yoshida, Yoshito Koyanagi, Masato Akiyama, Shoji Notomi, Shintaro Nakao, Toshio Hisatomi, Atsunobu Takeda, Eleftherios I. Paschalis, Demetrios G. Vavvas, Yasuhiro Ikeda, Koh-Hei Sonoda
Summary: Retinitis pigmentosa is an inherited disease that affects the eyes and can lead to blindness. Inflammatory monocytes play a key role in the progression of the disease. Treatment strategies that target these cells can potentially delay the progression of the disease.