Article
Neurosciences
Carola Rutigliani, James R. Tribble, Anna Hagstrom, Emma Lardner, Gauti Johannesson, Gustav Stalhammar, Pete A. Williams
Summary: Neuroinflammation is a crucial component of neurodegenerative diseases. The evidence for neuroinflammation in glaucoma patients is limited. By utilizing well-preserved wax embedded eyes, we confirmed the presence of significant neuroinflammatory responses in the retina and optic nerve head of glaucoma patients.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Cell Biology
James R. Tribble, Elizabeth Kastanaki, A. Bersan Uslular, Carola Rutigliani, Tim J. Enz, Pete A. Williams
Summary: This study demonstrates the potential of valproic acid in reducing retinal neuroinflammation and protecting retinal neurons. Valproic acid effectively reduces microglia and astrocyte inflammatory responses, and prevents the expression of pro-inflammatory cytokines in injured retina.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Syed A. H. Zaidi, Zhimin Xu, Tahira Lemtalsi, Porsche Sandow, Sruthi Athota, Fang Liu, Stephen Haigh, Yuqing Huo, S. Priya Narayanan, David J. R. Fulton, Modesto A. Rojas, Abdelrahman Y. Fouda, Robert W. Caldwell, Ruth B. Caldwell
Summary: This study demonstrates that cell-specific expression of A2 plays a neurotoxic role in optic nerve crush-induced retinal neurodegeneration. Deletion of A2 in neurons expressing Calb2 limits ONC-induced retinal neurodegeneration and improves visual function.
CELL DEATH & DISEASE
(2023)
Review
Biochemistry & Molecular Biology
Stefania Vernazza, Francesco Oddone, Sara Tirendi, Anna Maria Bassi
Summary: Glaucoma is a neurodegenerative disease that causes damage to retinal ganglion cells and results in permanent vision loss. While Intra Ocular Pressure (IOP) is the main therapeutic target, other pathological conditions and neuroprotective therapeutic approaches also play important roles in the disease progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Computer Science, Information Systems
Anita Manassakorn, Supatana Auethavekiat, Vera Sa-Ing, Sunee Chansangpetch, Kitiya Ratanawongphaibul, Nopphawan Uramphorn, Visanee Tantisevi
Summary: This study introduces a glaucoma diagnosis network named GlauNet, which utilizes convolutional neural network for feature extraction and classification, improving the accuracy of glaucoma diagnosis and demonstrating robustness against artifacts.
Article
Biochemistry & Molecular Biology
Zhou Zeng, Mengling You, Rong Rong, Cong Fan, Meini Chen, Haibo Li, Dan Ji, Xiaobo Xia
Summary: Glaucoma, the leading cause of blindness globally, lacks effective treatments due to limited understanding of its pathogenesis. This study investigated the role of non-coding RNAs (ncRNAs) in glaucoma and identified the Ier2/miR-1839/TSPO axis as critical to retinal damage and cell loss. Manipulating the expression of Ier2, miR-1839, and TSPO prevented retinal damage and cell loss. Furthermore, this axis regulated pyroptosis and apoptosis of retinal neurons through specific pathways. The study also found elevated TSPO expression in the brain and peripheral blood cells of glaucoma patients, suggesting its importance as a diagnostic and therapeutic target.
Article
Neurosciences
Sahil H. Shah, Lucio M. Schiapparelli, Satoshi Yokota, Yuanhui Ma, Xin Xia, Sahana Shankar, Sarah Saturday, Michael Nahmou, Catalina Sun, John Yates, Hollis T. Cline, Jeffrey L. Goldberg
Summary: In this study, a new in vivo quantitative measure of newly synthesized proteins was developed and applied to examine the changes in the retina after optic nerve injury. The results revealed a dynamic translational response within broader proteostasis regulation, enhancing our understanding of the cellular response to injury.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Chemistry, Multidisciplinary
Xuezhi Zhou, Rong Rong, Ganghao Liang, Haibo Li, Mengling You, Zhou Zeng, Haihua Xiao, Dan Ji, Xiao Xia
Summary: Glaucoma is a prominent cause of irreversible vision damage worldwide, but currently there is no effective treatment available. This study identified that overexpression of N-GSDMD protein can lead to pyroptosis in retinal ganglion cells (RGCs). A novel inhibitor called DSF, in combination with Cu(II), was found to significantly inhibit pyroptosis in RGCs. In vivo experiments showed that DSF-NPs+Cu(II) selectively inhibited pyroptosis in RGCs and provided a new therapeutic strategy for acute glaucoma.
Article
Biochemistry & Molecular Biology
Casey J. Keuthan, Julie A. Schaub, Meihan Wei, Weixiang Fang, Sarah Quillen, Elizabeth Kimball, Thomas V. Johnson, Hongkai Ji, Donald J. Zack, Harry A. Quigley
Summary: The level of intraocular pressure (IOP) is a major risk factor for glaucomatous optic neuropathy. This study found that the unmyelinated optic nerve region is differentially susceptible to IOP-induced damage compared to the myelinated region. Gene expression patterns in the unmyelinated optic nerve showed significant differences compared to the myelinated optic nerve and retina. Changes in gene expression induced by optic nerve injury were more extensive in the myelinated region than the unmyelinated region.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Lili Xie, Yuqin Yin, Larry Benowitz
Summary: CNTF gene therapy indirectly promotes optic nerve regeneration by increasing the expression of CCL5, and its beneficial effects are independent of CNTFRα but are affected by neutrophil and monocyte infiltration. Modulating the expression of CCR5 can also influence the effects of CNTF gene therapy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
James R. Tribble, Amin Otmani, Shanshan Sun, Sevannah A. Ellis, Gloria Cimaglia, Rupali Vohra, Melissa Joe, Emma Lardner, Abinaya P. Venkataraman, Alberto Dominguez-Vicent, Eirini Kokkali, Seungsoo Rho, Gauti Johnnesson, Robert W. Burgess, Peter G. Fuerst, Rune Brautaset, Miriam Kolko, James E. Morgan, Jonathan G. Crowston, Marcela Votruba, Pete A. Williams
Summary: Research has shown that nicotinamide has neuroprotective effects on neurons affected in glaucoma, preventing metabolic disruption and increasing oxidative phosphorylation in cells to reduce firing frequency of neurons.
Article
Cell Biology
Ben Mead, Alicia Kerr, Naoki Nakaya, Stanislav I. Tomarev
Summary: This study aimed to characterize the miRNA profile of purified retinal ganglion cells (RGC) from healthy and diseased rat retina. Over 100 different miRNAs were identified in diseased retina compared to healthy retina. Manipulating candidate mRNAs after retinal injury revealed significant neuroprotection and neuritogenesis effects in RGC.
Article
Cell Biology
Vittorio Porciatti, Tsung-Han Chou
Summary: This study introduces a framework to identify progressive and potentially reversible stages of RGC dysfunction leading to cell death in mouse models of glaucoma and other optic neuropathies. Mathematical equations are provided to describe state-transitions and modifiable parameters that can be used for hypothesis testing and fitting experimental PERG data. PERG dynamics are also utilized to differentiate phenotypic and altered RGC response dynamics, assess susceptibility to stressors, and evaluate reversible dysfunction with pharmacological treatment.
Article
Multidisciplinary Sciences
Mahmoud Fathy, Alia Noureldine, Hala M. Elmofty, Doaa Ahmad Tolba
Summary: This study investigates the impact of menopause and subsequent estrogen drop on optic nerve head structure and peripapillary vasculature. The results showed that postmenopausal women had significantly lower retinal nerve fiber layer thickness (RNFLT) and peripapillary vessel density (VD), and these measures were negatively correlated with age, hormonal drop, and intraocular pressure (IOP). The correlation between IOP and VD was stronger than its correlation with RNFLT. These findings suggest a link between hormonal changes after menopause and glaucoma in women, and highlight the potential of optical coherence tomography angiography (OCTA) in detecting early optic nerve damage.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Vittorio Porciatti, Tsung-Han Chou
Summary: Neuroprotection in optic neuropathies aims to preserve retinal ganglion cells and their function. The use of the Pattern Electroretinogram (PERG) for noninvasive evaluation of RGC function can provide diagnostic and prognostic value, as well as support early treatment recommendations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
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
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
Geriatrics & Gerontology
Morteza Abyadeh, Vivek Gupta, Joao A. Paulo, Samran Sheriff, Sina Shadfar, Matthew Fitzhenry, Ardeshir Amirkhani, Veer Gupta, Ghasem H. Salekdeh, Paul A. Haynes, Stuart L. Graham, Mehdi Mirzaei
Summary: Alzheimer's disease is an incurable form of dementia that presents a major medical, social, and economic challenge worldwide. Pathological features associated with Alzheimer's disease have also been observed in retinal neurodegenerative diseases. The involvement of Apolipoprotein E in these diseases is important.
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)