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
Cell Biology
Sean Mccracken, Michael J. Fitzpatrick, Allison L. Hall, Zelun Wang, Daniel Kerschensteiner, Josh L. Morgan, Philip R. Williams
Summary: Retinal ganglion cell (RGC) degeneration, caused by axon degeneration, is the main reason for vision loss in blinding conditions. Axonal Ca2+ elevations from optic nerve injury do not reach RGC somas, and baseline Ca2+ levels of RGCs predict their survival after axon injury.
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
Biochemistry & Molecular Biology
Jacky M. K. Kwong, Joseph Caprioli, Joanne C. Y. Lee, Yifan Song, Feng-Juan Yu, Jingfang Bian, Ying-Hon Sze, King-Kit Li, Chi-Wai Do, Chi-Ho To, Thomas Chuen Lam
Summary: This study investigated the proteomic changes in the retina after optic nerve transection in rats. Using high-resolution mass spectrometry, they identified several differentially expressed proteins related to retinal ganglion cell damage, such as ALDH1A1 and SNCG.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Nicole A. Muench, Sonia Patel, Margaret E. Maes, Ryan J. Donahue, Akihiro Ikeda, Robert W. Nickells
Summary: Mitochondrial function and dysfunction play important roles in neurodegeneration, especially in RGCs which are highly vulnerable due to their unique structure. Glaucoma represents a combination of events at the optic nerve head that increase metabolic stress on RGC axons, leading to axonal transport failure. Additionally, RGCs are sensitive to genetic mutations affecting mitochondrial dynamics and clearance, often resulting in optic neuropathy as the sole pathological defect.
Article
Immunology
Feifei Wang, Yuning Song, Peiyu Liu, Fangli Ma, Zhida Peng, Yulian Pang, Haijian Hu, Ling Zeng, Hongdou Luo, Xu Zhang
Summary: This study aimed to confirm the effect of intravitreal injection of RAPA on RGCs and explore the underlying mechanism. The results showed that RAPA reduced the activation of glial cells and inhibited the expression of inflammatory factors in the retina. Furthermore, RAPA exerted protective effects on RGC axons by inhibiting glial activation and regulating the mTOR/ROCK pathway.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Ling-Ping Cen, Tsz Kin Ng, Jia-Jian Liang, Ciyan Xu, Xi Zhuang, Yu-Fen Liu, Shao-Lang Chen, Yanxuan Xu, Qichen Yang, Xiang-Ling Yuan, Yong Jie Qin, Sun On Chan, Haoyu Chen, Mingzhi Zhang, Andrew V. Schally, Chi Pui Pang
Summary: The study demonstrated that both agonists and antagonists of GHRH could promote the survival of RGCs through increasing Akt phosphorylation and regulating the expression of inflammation-related genes. GHRH analogs not only have a protective effect on RGCs after optic nerve injury, but also enhance the activation of macrophages.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biochemistry & Molecular Biology
Jess Rhee, Kendrick Co Shih
Summary: The review of gene-based therapy for RGC neuroprotection showed promising results utilizing AAV vectors encoding specific genes. However, challenges still exist, such as the acute nature of injury models in studies and the regulation of gene expression.
Article
Neurosciences
Yuan Liu, Rossana Cheng He, Gustavo C. Munguba, Richard K. Lee
Summary: Glaucoma is one of the main causes of irreversible visual field loss and blindness worldwide. This study found that the expression level of PVALB decreases with RGC degeneration, indicating that PVALB is a reliable RGC molecular marker.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Heung-Sun Kwon, Karl Kevala, Haohua Qian, Mones Abu-Asab, Samarjit Patnaik, Juan Marugan, Hee-Yong Kim
Summary: Functional recovery after axonal injury in the adult central nervous system is extremely difficult. Activation of G-protein coupled receptor 110 (GPR110, ADGRF1) has been found to stimulate neurite extension in developing neurons and after axonal injury in adult mice. This study demonstrates that GPR110 activation partially restores impaired visual function caused by optic nerve injury in adult mice. Intravitreal injection of GPR110 ligands significantly reduces axonal degeneration and improves axonal integrity and visual function, indicating that targeting GPR110 may be a viable strategy for functional recovery after optic nerve injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Pedro Henrique Victorino, Camila Marra, Dumitru Andrei Iacobas, Sanda Iacobas, David C. Spray, Rafael Linden, Daniel Adesse, Hilda Petrs-Silva
Summary: Glaucoma is a complex neurodegenerative disease involving degeneration of retinal ganglion cells. A study on the transcriptome of rat retina post-optic nerve crush revealed changes in gene expression variability and coordination, particularly in pathways related to complement cascade and Notch signaling. This deep bioinformatic analysis provides novel insights into the molecular mechanisms underlying RGC degeneration and retinal remodeling after ONC.
Article
Ophthalmology
Tae Kyeom Kang, Tam Thi Le, Kyung-A Kim, Young-Joo Kim, Wook-Bin Lee, Sang Hoon Jung
Summary: Lithospermum erythrorhizon has potent wound healing, antiinflammatory, and antioxidant properties. Extracts from this plant have been shown to protect retinal cells in vitro and in vivo, with lithospermic acid A identified as a key compound responsible for its antioxidant effects. This suggests that Lithospermum erythrorhizon could be a beneficial agent for treating retinal degenerative diseases such as glaucoma.
EXPERIMENTAL EYE RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Yi-Fen Lai, Ting-Yi Lin, Pin-Kuan Ho, Yi-Hao Chen, Yu-Chuan Huang, Da-Wen Lu
Summary: In this review, the neuroprotective function of erythropoietin (EPO) in extra-hematopoietic tissues, especially the retina, is highlighted. The available pre-clinical studies of EPO in treating various optic neuropathies are summarized. Furthermore, future strategies for optic nerve protection and repair using EPO and its derivatives are explored.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Shun Masuda, Shigeru Tanaka, Hiroko Shiraki, Yusuke Sotomaru, Kana Harada, Izumi Hide, Yoshiaki Kiuchi, Norio Sakai
Summary: The expression of GPR3 in retinal ganglion cells (RGCs) plays an important role in axonal regeneration and neuronal survival. Knocking out the GPR3 gene makes RGCs more vulnerable to neural death, while upregulation of GPR3 accelerates axonal regeneration.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Neurosciences
James R. Tribble, Anna Hagstrom, Kenza Jusseaume, Emma Lardner, Raymond Ching-Bong Wong, Gustav Stalhammar, Pete A. Williams
Summary: Glaucoma, the leading cause of irreversible blindness, lacks effective treatments targeting the neurodegenerative component. Utilizing RNA sequencing data and antibody labeling in human eyes, the study identified that retinal ganglion cells express the NAD salvage pathway, particularly the enzyme NMNAT2, which declines in glaucoma. This suggests that retinal ganglion cells can utilize nicotinamide and offers potential for clinical trials in glaucoma.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)