Review
Neurosciences
Jennifer H. Pham, Dorota L. Stankowska
Summary: Glaucoma is a leading cause of blindness worldwide and is commonly associated with elevated intraocular pressure. Recent studies suggest that mitochondrial dysfunction plays a crucial role in glaucomatous neurodegeneration. The retina, especially the retinal ganglion cells (RGCs), relies heavily on mitochondrial energy for signal transduction, making them vulnerable to oxidative damage. Mitochondrial dysfunction and ER stress have been observed in RGCs in glaucoma models, and the potential cross-signaling and roles of MAMs need to be further investigated.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Cell Biology
Yanqiao Huang, Miner Yuan, Fang Duan, Yao Yang, Bingsheng Lou, Xiaofeng Lin
Summary: The study showed that the inhibition of ER stress by 4-PBA can alleviate inflammation and protect the retina and RGCs from injury in an OAB mouse model. This suggests that 4-PBA may have therapeutic potential for treating OAB.
INFLAMMATION RESEARCH
(2022)
Article
Multidisciplinary Sciences
Wei Chen, Pingting Liu, Dong Liu, Haoliang Huang, Xue Feng, Fang Fang, Liang Li, Jian Wu, Liang Liu, David E. Solow-Cordero, Yang Hu
Summary: This study found that the FDA-approved drug maprotiline inhibits histamine receptor H1-mediated ER stress and provides significant neuroprotection in a mouse glaucoma model. Inhibition of ER stress shows potential for neuroprotection.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Rong Li, Yao Wang, Pei Chen, Jiamin Meng, Hongbing Zhang
Summary: The activation of G-protein coupled estrogen receptor (GPER) can protect the survival of retinal ganglion cells (RGCs) in the early stage of retinopathy of prematurity (ROP) by reducing endoplasmic reticulum (ER) stress under hyperoxia.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Endocrinology & Metabolism
Chao Wang, Yaqiong An, Zhaohua Xia, Xuezhi Zhou, Haibo Li, Shuang Song, Lexi Ding, Xiaobo Xia
Summary: This study found that melatonin could protect RGCs from glutamate excitotoxicity and NMDA-induced injury, reduce oxidative stress, and improve visual function in mice. These findings provide practical research ideas for the comprehensive prevention and treatment of glaucoma using melatonin.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Xue Yang, Xiaowei Yu, Zhenni Zhao, Yuqing He, Jiamin Zhang, Xiaoqian Su, Nannan Sun, Zhigang Fan
Summary: Repeated transient spike in intraocular pressure (IOP) leads to retinal ganglion cell damage and apoptosis in a mouse model, with endoplasmic reticulum (ER) stress implicated in the molecular mechanism. This study highlights the detrimental effects of Spike IOP on the retina and the role of ER stress in retinal cell apoptosis.
JOURNAL OF ZHEJIANG UNIVERSITY-SCIENCE B
(2021)
Article
Environmental Sciences
Zaiwei Wu, Fang Wang, Liwen Hu, Jianrong Zhang, Daojun Chen, Sujuan Zhao
Summary: This study demonstrates that MCLR causes damage to the male reproductive system and enhances autophagy, indicating the essential role of autophagy in MCLR-induced cell death. Furthermore, the study reveals the involvement of ER stress-related autophagy pathway in MCLR-induced apoptosis and injury in the male reproductive system.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)
Article
Ophthalmology
Kwanghyun Lee, Jin-Ok Choi, Ahreum Hwang, Hyoung Won Bae, Chan Yun Kim
Summary: This study investigated the protective effects of astrocyte-derived CNTF on retinal ganglion cells (RGCs) and identified the signaling pathways involved. The results showed that astrocytes improved RGC viability and /33-tubulin expression, and the concentration of CNTF increased in the RGC-astrocyte co-culture medium. The protective effects of astrocytes were dependent on CNTF, suggesting its importance in mediating these effects. CNTF treatment alone also enhanced RGC viability and /33-tubulin expression, and increased the population of viable RGCs under oxidative stress. Different pathways, such as PI3K/AKT, JAK/STAT, and MAPK/ERK, were found to be associated with RGC viability and /33-tubulin expression. RNA sequencing revealed the genes upregulated and downregulated by CNTF treatment, providing insights into the molecular mechanisms involved in the protective effects. In conclusion, this study highlights the importance of astrocyte-derived CNTF in protecting RGCs and identifies novel genes and pathways associated with this protective effect. It may contribute to the development of treatments for RGC injury.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Pharmacology & Pharmacy
Xiaojing Fu, Wenwen Zhao, Kangkang Li, Jingyi Zhou, Xuehong Chen
Summary: The study reveals the anticancer effects of cryptotanshinone (CPT) in colorectal cancer (CRC) by activating autophagy signaling mediated by ER stress. CPT selectively inhibits the growth and proliferation of HCT116 and SW620 cells while having little effect on SW480 cells.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Environmental Sciences
Qiaoni Hu, Jifang Zheng, Xiao Na Xu, Chaohao Gu, Wanting Li
Summary: Uranium contamination induces excessive intracellular reactive oxygen species (ROS) generation, which is considered as a possible mediator of kidney tubular cells injury and nephrotoxicity. This study found that U exposure triggers endoplasmic reticulum stress, apoptosis, and down-regulation of PI3K/AKT/mTOR signaling. Administration of antioxidant N-acetylcysteine (NAC) effectively blocks ROS generation, ER stress, and apoptosis, and reverses the down-regulation of phosphorylated PI3K induced by U exposure.
ENVIRONMENTAL TOXICOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Ciriaco Corral-Domenge, Pedro de la Villa, Alicia Mansilla, Francisco Germain
Summary: The retina, as part of the central nervous system, is crucial for understanding the health and functioning of both the retina itself and the entire central nervous system. The neurons known as ganglion cells are responsible for processing and transmitting light information, and the degeneration of these cells can lead to irreversible blindness or impaired vision. Research into the subtypes of these ganglion cells and the identification of cell death pathways is essential for understanding degenerative processes and developing prevention strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Jinzi Zhou, Fenghua Chen, Aimin Yan, Jian Jiang, Xiaobo Xia
Summary: The study found that endoplasmic reticulum stress is the underlying cause of glaucoma, which can promote the apoptosis of RGCs in diabetic mice.
TRANSPLANT IMMUNOLOGY
(2022)
Article
Environmental Sciences
Meng Li, Jing Feng, Ying Cheng, Nisha Dong, Xiaolin Tian, Penghui Liu, Yannan Zhao, Yulan Qiu, Fengjie Tian, Yi Lyu, Qian Zhao, Cailing Wei, Meng Wang, Jiyu Yuan, Xiaodong Ying, Xuefeng Ren, Xiaoyan Yan
Summary: Exposure to arsenic and fluoride induced early apoptosis and endoplasmic reticulum expansion in myocardial cells. Endoplasmic reticulum stress (ERS) and apoptosis pathways were involved in the damage caused by co-exposure to arsenic and fluoride.
Article
Agriculture, Dairy & Animal Science
Jun Bai, Jun Li, Ning Liu, Hai Jia, Xuemeng Si, Yusong Zhou, Zhian Zhai, Ying Yang, Fazheng Ren, Zhenlong Wu
Summary: This study investigated the toxicological effect and mechanism of Zearalenone (ZEA) exposure on reproduction in pigs during early stages of pregnancy. It was found that ZEA can cause cell cycle arrest, apoptosis, endoplasmic reticulum (ER) stress, and autophagy in trophoblast ectoderm cells. Furthermore, inhibiting ER stress can reduce cell death, suggesting a critical role of ER stress in the activation of autophagy.
Review
Cell Biology
Wen-juan Zhao, Chun-ling Fan, Xi-min Hu, Xiao-xia Ban, Hao Wan, Ye He, Qi Zhang, Kun Xiong
Summary: Glaucoma is a group of diseases that result in degeneration of retinal ganglion cells (RGCs) and progressive, irreversible vision loss. High intraocular pressure (IOP) increases the risk of glaucoma and is associated with RGC loss. Lowering IOP is the current focus of glaucoma therapy; however, RGC and visual loss may still persist even with well-controlled IOP. Therefore, discovering neuroprotective strategies for RGCs that are independent of IOP is crucial for effective glaucoma management. Investigating the mechanisms of RGC death and finding ways to counteract its effects is a promising direction for glaucoma control. Empirical studies have revealed the role of regulated cell death pathways in RGC death in glaucoma. This review explores the RCD of RGCs following elevated IOP and optic nerve damage and discusses the significant benefits of mitigating RCD in preserving visual function.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Soumalya Sarkar, Vivek K. Gupta, Samridhi Sharma, Ting Shen, Veer Gupta, Mehdi Mirzaei, Stuart L. Graham, Nitin Chitranshi
Summary: Alterations in RXR signalling are associated with neurodegenerative disorders. This study identified deleterious SNPs that affect the structure and function of RXR isoforms. Seven missense mutations were found in RXR isoforms, including two novel mutations. In silico prediction tools were used to assess the pathogenicity and stability of RXR mutations. The analysis showed a mix of conclusive and inconclusive genotype-phenotype correlations.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Devaraj Basavarajappa, Vivek Gupta, Roshana Vander Wall, Veer Gupta, Nitin Chitranshi, Seyed Shahab Oddin Mirshahvaladi, Viswanthram Palanivel, Yuyi You, Mehdi Mirzaei, Alexander Klistorner, Stuart L. Graham
Summary: Glaucoma is a complex neurodegenerative disease characterized by optic nerve damage and apoptotic retinal ganglion cell (RGC) death. Our study demonstrated that activation of neuronal S1PR1 with siponimod treatment can exert neuroprotection in glaucoma by upregulating Akt and Erk1/2 activation and suppressing the apoptotic signaling via modulation of the c-Jun/Bim cascade and increasing Bad phosphorylation. Conversely, deletion of S1PR1 in RGCs diminished the neuroprotective effects of siponimod treatment. These findings suggest that S1PR1 is a potential therapeutic target for neuroprotection in glaucoma.
Article
Cell Biology
Devaraj Basavarajappa, Vivek Gupta, Nitin Chitranshi, Roshana Vander Wall, Rashi Rajput, Kanishka Pushpitha, Samridhi Sharma, Mehdi Mirzaei, Alexander Klistorner, Stuart Graham
Summary: The S1PR1 signaling pathway plays a crucial role in the survival of retinal ganglion cells and neurons in the dorsolateral geniculate nucleus. Siponimod, as a modulator of S1PR1, exerts direct neuroprotective effects in neurons in the central nervous system, independent of its peripheral immunomodulatory effects.
NEURAL REGENERATION RESEARCH
(2023)
Article
Clinical Neurology
Yosef Koronyo, Altan Rentsendorj, Nazanin Mirzaei, Giovanna C. Regis, Julia Sheyn, Haoshen Shi, Ernesto Barron, Galen Cook-Wiens, Anthony R. Rodriguez, Rodrigo Medeiros, Joao A. Paulo, Veer B. Gupta, Andrei A. Kramerov, Alexander V. Ljubimov, Jennifer E. Van Eyk, Stuart L. Graham, Vivek K. Gupta, John M. Ringman, David R. Hinton, Carol A. Miller, Keith L. Black, Antonino Cattaneo, Giovanni Meli, Mehdi Mirzaei, Dieu-Trang Fuchs, Maya Koronyo-Hamaoui
Summary: Pathologies of Alzheimer’s disease (AD) can be found in the neurosensory retina, but their exact nature and distribution in relation to disease progression in the brain are still largely unknown. This study conducted extensive histopathological and biochemical investigations of postmortem retina and brain tissues from 86 human donors to better understand the pathological features of AD in the retina. The findings suggest a quantitative relationship between retinopathy, brain pathology, and cognitive impairment, and may lead to the development of reliable retinal biomarkers for noninvasive screening and monitoring of AD.
ACTA NEUROPATHOLOGICA
(2023)
Article
Clinical Neurology
Haoshen Shi, Yosef Koronyo, Dieu-Trang Fuchs, Julia Sheyn, Ousman Jallow, Krishna Mandalia, Stuart L. Graham, Vivek K. Gupta, Mehdi Mirzaei, Andrei A. Kramerov, Alexander V. Ljubimov, Debra Hawes, Carol A. Miller, Keith L. Black, Roxana O. Carare, Maya Koronyo-Hamaoui
Summary: This study found that vascular amyloid beta (Aβ) protein deposits were detected in retinas of mild cognitively impaired (MCI) and Alzheimer's disease (AD) patients, and these deposits were linked to disease status. The study also revealed that the components of retinal vascular tight junctions (TJs) and Aβ expression were correlated with neuropathology. The severe decreases in retinal vascular zonula occludens-1 (ZO-1) and claudin-5 were identified in MCI and AD patients, which correlated with arteriolar Aβ(40) deposition and cerebral pathology and cognitive deficits.
ALZHEIMERS & DEMENTIA
(2023)
Article
Biotechnology & Applied Microbiology
Nitin Chitranshi, Rashi Rajput, Angela Godinez, Kanishka Pushpitha, Mehdi Mirzaei, Devaraj Basavarajappa, Veer Gupta, Samridhi Sharma, Yuyi You, Giovanna Galliciotti, Ghasem H. Salekdeh, Mark S. Baker, Stuart L. Graham, Vivek K. Gupta
Summary: Our research shows that oxidation deactivation impairs the inhibitory activity of the serine protease inhibitor neuroserpin (NS) in glaucoma. The loss of NS is detrimental to retinal structure and function, and perturbations in autophagy and microglial and synaptic markers are associated with NS ablation. On the other hand, upregulation of NS promotes retinal ganglion cell (RGC) survival and protects against glaucoma-induced degeneration.
Article
Cell Biology
Samran Sheriff, Ting Shen, Sandra Abdal, Danit Saks, Mehdi Mirzaei, Veer Gupta, Nitin Chitranshi, Yuyi You, Angela Schultz, Stuart Graham, Vivek Gupta
Summary: Examining retinal tissue provides a unique method to quantify Alzheimer's disease-related changes. This meta-analysis investigated optical coherence tomography parameters and discovered that Alzheimer's disease patients had lower retinal nerve fiber layer thickness and thinner macular parameters compared to controls. Optical coherence tomography angiography parameters showed mixed results between Alzheimer's disease and controls. Overall, our findings suggest that optical coherence tomography technology can detect retinal and microvascular changes in Alzheimer's disease patients and aid in monitoring and early diagnosis.
NEURAL REGENERATION RESEARCH
(2023)
Article
Neurosciences
Faezeh Shekari, Morteza Abyadeh, Anna Meyfour, Mehdi Mirzaei, Nitin Chitranshi, Vivek Gupta, Stuart L. Graham, Ghasem Hosseini Salekdeh
Summary: A large number of people around the world suffer from visual impairment, and the available therapies focus on preventing the progression of eye disorders. This review explores the potential of using extracellular vesicles (EVs) as a regenerative therapy for eye-related complications. The review examines the current knowledge about EVs and their therapeutic applications, as well as the challenges in translating EV-based therapy into clinical settings.
PROGRESS IN NEUROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Liting Deng, Vivek Gupta, Morteza Abyadeh, Nitin Chitranshi, Kanishka Pushpitha, Yunqi Wu, Veer Gupta, Yuyi You, Joao A. Paulo, Stuart L. Graham, Mehdi Mirzaei, Paul A. Haynes
Summary: Photoreceptor cells are highly vulnerable to oxidative stress, which plays a key role in ocular diseases leading to retinal degeneration and blindness. A mass-spectrometric study using TMT labelling revealed proteome changes in photoreceptor cells following oxidative stress induction. Differential expression of proteins involved in various pathways was observed in response to oxidative stress, including ECM receptor interaction, oxidative phosphorylation, and spliceosome pathways.
Article
Ophthalmology
Danit G. Saks, Angela Schulz, Ayub Qassim, Henry Marshall, Alex W. Hewitt, Stuart Macgregor, Jamie E. Craig, Stuart L. Graham
Summary: Individuals with a higher genetic risk of glaucoma are more likely to have retinal vascular defects and structural glaucomatous loss, but this is not related to systemic cardiovascular risk.
ACTA OPHTHALMOLOGICA
(2023)
Article
Neurosciences
Devaraj Basavarajappa, Vivek Gupta, Nitin Chitranshi, Deepa Viswanathan, Veer Gupta, Roshana Vander Wall, Viswanthram Palanivel, Mehdi Mirzaei, Yuyi You, Alexander Klistorner, Stuart L. Graham
Summary: Glaucoma is a major cause of permanent blindness worldwide, characterized by neurodegeneration and neuroinflammation. Siponimod, an immunomodulatory drug, has shown protective effects against acute NMDA excitotoxicity in the retina. Activation of glial cells, inflammatory pathways, and the NLRP3 inflammasome were suppressed with siponimod treatment. These findings suggest that siponimod has anti-inflammatory effects and could be a potential therapeutic strategy for neuroinflammatory conditions.
MOLECULAR NEUROBIOLOGY
(2023)
Review
Geriatrics & Gerontology
Zhuang-Yao D. Wei, Ketty Liang, Ashok K. Shetty
Summary: SARS-CoV-2 uses a spike protein to enter human cells by binding to ACE-2, resulting in COVID-19. COVID-19 primarily causes respiratory infection and can lead to severe systemic inflammation. Neurological symptoms are also common in some patients.
Review
Biochemistry & Molecular Biology
Devaraj Basavarajappa, Caridad Galindo-Romero, Vivek Gupta, Marta Agudo-Barriuso, Veer B. Gupta, Stuart L. Graham, Nitin Chitranshi
Summary: In this review, the recent research progress on the degenerative mechanisms of retinal ganglion cells (RGCs) in glaucoma is discussed. High intraocular pressure is not the sole factor contributing to glaucoma pathogenesis. The balance of pro-survival and pro-death signaling pathways in the retina strongly influences RGC function and survival. Various molecules and regulated cell death pathways are involved in the development of glaucoma.
MOLECULAR ASPECTS OF MEDICINE
(2023)
