Article
Cell Biology
Luming Guo, Xiaoling Xie, Jing Wang, Haiyan Xiao, Shuchun Li, Mei Xu, Ebenezer Quainoo, Rithwik Koppaka, Jiaping Zhuo, Sylvia B. Smith, Lin Gan
Summary: The generation and characterization of a knock-in mouse line, Rbpms-CreER(T2), that allows for the conditional activation of a reporter gene in retinal ganglion cells (RGCs) is reported. The knock-in mice showed efficient recombination and no detectable defects, making them a powerful tool for studying RGCs.
Article
Biochemistry & Molecular Biology
Audrey Voisin, Afsaneh Gaillard, Anais Balbous, Nicolas Leveziel
Summary: This study found that retinal pigment epithelial (RPE) cells from patients with age-related macular degeneration (AMD) exhibit altered phagocytic activity. The researchers also identified genes related to the mTOR/PI3K-AKT/MEK-ERK pathway that are involved in phagocytosis. These findings indicate a typical disease phenotype in RPE cells from AMD patients.
Article
Biochemistry & Molecular Biology
Zuberwasim Sayyad, Sreeram Kaveti, Debanjan Bhattacharjee, Dhiviya Vedagiri, Nishant Jain, Ghanshyam Swarup
Summary: M98K-OPTN is associated with normal tension glaucoma and interacts with TNF alpha polymorphism in causing glaucoma. It sensitizes retinal cells to TNF alpha and ER stress-induced cell death, and alters ER stress response signaling. These findings support the hypothesis that M98K-OPTN may contribute to retinal ganglion cell death associated with glaucoma.
Article
Biochemistry & Molecular Biology
Jae-Byoung Chae, Chul-Woo Park, Hyeong Min Lee, Leo Sungwong Choi, Chaehee Park, Junghoon Kim, Jaejin Shin, Jooseung Hyeon, Jihan Lee, Hyungwoo Lee, Hyung Soon Park, Chang-Hoon Nam, Hyewon Chung
Summary: The study reveals an association between cellular senescence and RPE/retinal degeneration, while suggesting the use of Zmpste24-/- mice as a novel senescent RPE model for AMD.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Ye Liu, Di Wu, Qiuli Fu, Shengjie Hao, Yuzhou Gu, Wei Zhao, Shuying Chen, Feiyin Sheng, Yili Xu, Zhiqing Chen, Ke Yao
Summary: Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the elderly population. The underlying molecular mechanisms of how retinal pigment epithelial (RPE) cells respond and progress under oxidative damage are still largely unknown. This study reveals the significance of Glutathione specific gamma-glutamylcyclotransferase 1 (Chac1) as a novel contributor of oxidative-stress-induced ferroptosis in RPE, suggesting its potential role in AMD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Geetika Kaur, Nikhlesh K. Singh
Summary: Retinal neurodegeneration, commonly manifested as apoptosis or impaired function of photoreceptors, is a major cause of irreversible vision loss and blindness. This review summarizes the extensive research conducted on the pathogenesis and treatment of retinal degenerative diseases, including age-related macular degeneration, inherited retinal dystrophies, retinitis pigmentosa, Stargardt macular dystrophy, and Leber congenital amaurosis. The role of inflammation in retinal degeneration is highlighted, and various therapeutic approaches, such as gene therapy and stem cell-based therapies, are evaluated.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Annamaria Tisi, Fanny Pulcini, Giulia Carozza, Vincenzo Mattei, Vincenzo Flati, Maurizio Passacantando, Cinzia Antognelli, Rita Maccarone, Simona Delle Monache
Summary: The study demonstrates that cerium oxide nanoparticles can counteract retinal neovascularization induced by oxidative damage, suggesting a potential new therapeutic strategy for wet AMD treatment.
Review
Biochemistry & Molecular Biology
Alexa Klettner, Johann Roider
Summary: TLR activation in the retinal pigment epithelium (RPE) can induce a pro-inflammatory response, leading to inflammation by triggering the release of pro-inflammatory cytokines, impairing RPE function, and causing RPE cell degeneration. This constant cycle of TLR activation may contribute to the development of AMD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Aram Asatryan, Jorgelina M. Calandria, Marie-Audrey I. Kautzmann, Bokkyoo Jun, William C. Gordon, Khanh V. Do, Surjyadipta Bhattacharjee, Thang L. Pham, Vicente Bermudez, Melina Valeria Mateos, Jessica Heap, Nicolas G. Bazan
Summary: A new cell line ABC derived from human RPE cells was characterized in this study, which remarkably recapitulates the characteristics of native human eye cells. These cells display higher resistance to oxidative stress and can be protected from senescence through mTOR inhibition. They are also responsive to Neuroprotectin D1, which downregulates inflammasomes and upregulates antioxidant and anti-inflammatory genes.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Medicine, General & Internal
Shinichiro Chujo, Hisashi Matsubara, Yoshitsugu Matsui, Masahiko Sugimoto, Mineo Kondo
Summary: The purpose of this study was to determine if atrophy of the retinal pigment epithelium (RPE) in eyes with neovascular age-related macular degeneration (nAMD), which meets the criteria for suspension of anti-vascular endothelial growth factor (anti-VEGF) treatment, is associated with anti-VEGF treatments. The results indicated that the expansion rate of RPE atrophy did not differ significantly between eyes that continued anti-VEGF treatment and those that suspended treatment.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Blanca Chinchilla, Rosario Fernandez-Godino
Summary: Changes in the Bruch's membrane can lead to age-related macular degeneration, with abnormal ECM leading to epithelial mesenchymal transition in RPE cells. Understanding these processes may lead to the development of new therapies for AMD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Ophthalmology
Stephanie M. George, Fangfang Lu, Mishal Rao, Lyndsay L. Leach, Jeffrey M. Gross
Summary: Diseases causing retinal pigment epithelium degeneration, such as age-related macular degeneration, are a leading cause of blindness worldwide. Current therapies for RPE regeneration are ineffective, highlighting the need for further research into the regenerative mechanisms of RPE.
PROGRESS IN RETINAL AND EYE RESEARCH
(2021)
Article
Neurosciences
Claudia Ingensiep, Kim Schaffrath, Peter Walter, Sandra Johnen
Summary: Glaucoma is a heterogeneous eye disease characterized by atrophy of the optic nerve head. A study using a multielectrode array-based ex vivo glaucoma acute model found that high hydrostatic pressure did not affect the functionality of retinal ganglion cells (RGCs), but significantly changed their bursting behavior. The findings suggest that RGCs are tolerant to high short-term pressure stress.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Jiyang Cai, Christopher Litwin, Rui Cheng, Jian-Xing Ma, Yan Chen
Summary: mTORC1, an important regulator in cell metabolism and stress response, has been found to play a pathogenic role in age-related macular degeneration (AMD). In this study, a previously unknown signaling protein called DARPP-32, regulated by mTORC1, was identified and found to contribute to the degeneration of retinal pigment epithelium (RPE) in AMD.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Parameswaran G. Sreekumar, Deborah A. Ferrington, Ram Kannan
Summary: Glutathione (GSH) plays a crucial role as a cellular antioxidant in tissues, including the retina. Recent research has highlighted the importance of mitochondrial GSH in maintaining retinal pigment epithelium cell bioenergetics and health.
Article
Ophthalmology
Katie L. Topping, Angelica Ortiz, Jonathan H. Lin, Andrea L. Kossler
Summary: Radiation-induced malignancy is rare, with sarcomas and squamous cell carcinomas being common types. In this case, a 74-year-old woman presented with redness and swelling in the right periorbital region, ultimately undergoing orbital exenteration due to a rare hyalinizing clear cell carcinoma. This highlights the importance of lifetime monitoring for patients who have undergone radiation therapy.
OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY
(2021)
Article
Ophthalmology
Victor A. Eng, Jonathan H. Lin, Prithvi Mruthyunjaya, Benjamin P. Erickson
Summary: The authors report a rare case of lung adenocarcinoma metastasis to the lacrimal sac, underscoring the importance of comprehensive oncologic surveillance.
OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY
(2021)
Article
Neurosciences
Helen Zhao, Jonathan Lin, Gary Sieck, Gabriel G. Haddad
Summary: Chronic mountain sickness (CMS) is a disease that affects high-altitude populations living above 2,500 m, causing severe hypoxemia, excessive erythrocytosis, and neurological deficits. The cellular mechanisms of CMS neuropathology are still unknown, but it involves altered mitochondrial dynamics and increased susceptibility to hypoxia-induced cell death. Activation of Akt and overexpression of Parkin can protect non-CMS neurons from hypoxia-induced cell death, while CMS neurons lack Akt activation and Parkin expression, rendering them more vulnerable.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Ophthalmology
Michael D. Yu, Clara J. Men, Huy Do, A. Dimitrios Colevas, Jonathan H. Lin, Peter R. Egbert, David T. Tse, Andrea L. Kossler
Summary: In this study, we reported a case of lacrimal gland adenoid cystic carcinoma treated with neoadjuvant intra-arterial chemotherapy. We evaluated the treatment response using a combination of genome sequencing and immunohistochemical evaluation, which showed tumor apoptosis and a decrease in variant allele frequency of the NOTCH1 mutation. This suggests that NOTCH1 analysis could be a potential marker of cisplatin sensitivity.
OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY
(2022)
Article
Multidisciplinary Sciences
Heike Kroeger, Julia M. D. Grandjean, Wei-Chieh Jerry Chiang, Daphne D. Bindels, Rebecca Mastey, Jennifer Okalova, Amanda Nguyen, Evan T. Powers, Jeffery W. Kelly, Neil J. Grimsey, Michel Michaelides, Joseph Carroll, R. Luke Wiseman, Jonathan H. Lin
Summary: ER stress and UPR signaling contribute to human diseases, including severe congenital vision loss conditions like achromatopsia. Loss-of-function ATF6 variants lead to defective cone formation in the retina, highlighting the essential role of ATF6 in human cone development. Pharmacologic targeting of the ATF6 pathway may hold potential for treating blinding retinal diseases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Ophthalmology
Ahmad Al-Moujahed, Jonathan H. Lin, Michael R. Gagnon, Jose Pulido, Prithvi Mruthyunjaya, Jesse J. Jung
Summary: This study reported the clinicopathologic correlation of a case of bilateral serpiginous-like chorioretinitis associated with unilateral ciliochoroidal melanoma. The findings suggest that serpiginous-like chorioretinitis may present as a paraneoplastic, predominantly T-lymphocyte inflammation associated with intraocular tumors such as uveal melanoma.
RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES
(2022)
Article
Ophthalmology
Saman S. Ahmadian, Ian J. Dryden, Andrea Naranjo, Angus Toland, Romain A. Cayrol, Donald E. Born, Peter S. Egbert, Ryanne A. Brown, Prithvi Mruthyunjaya, Jonathan H. Lin
Summary: In this study, we evaluated the expression of PRAME in UM patients using both RT-PCR and IHC techniques. The results showed that PRAME IHC can distinguish PRAME-positive and PRAME-negative UM tumor cells, and also revealed intratumoral heterogeneity in PRAME expression. The concordance between PRAME RT-PCR and IHC results was observed in the majority of cases.
OCULAR ONCOLOGY AND PATHOLOGY
(2022)
Article
Ophthalmology
Vanessa S. Goodwill, Ian Dryden, Jihee Choi, Chiara De Lillo, Katrin Soldau, Jorge Llibre-Guerra, Henry Sanchez, Christina J. Sigurdson, Jonathan H. Lin
Summary: This study analyzed the histopathology and morphology of PrPSc deposits in the retina and brain of sCJD patients. The findings showed that the morphology of retinal PrPSc deposits is different from brain deposits, and they are not associated with neurodegenerative changes typically seen in the brain.
EXPERIMENTAL EYE RESEARCH
(2022)
Article
Multidisciplinary Sciences
Kyle Kim, Lance A. Safarta, Wei-Chieh J. Chiang, Judith A. Coppinger, Eun-Jin Lee, Jonathan H. Lin
Summary: This study compared the protein interaction partners of P23H rhodopsin and wild-type rhodopsin using mass spectrometry and identified important proteins associated with P23H rhodopsin. The P23H rhodopsin protein interactome showed loss of phototransduction and gain of ubiquitin-related proteins, as well as enrichment of gene ontology terms related to ER-associated protein degradation, ER stress, and translation.
SCIENTIFIC REPORTS
(2022)
Article
Pathology
Eun-Jin Lee, Monica S. Diaz-Aguilar, Hyejung Min, Jihee Choi, Diego A. Valdez Duran, Julia M. Grandjean, R. Luke Wiseman, Heike Kroeger, Jonathan H. Linyz
Summary: This study analyzed the transcriptomes of retinal organoids from ACHM patients with ATF6 variants in order to investigate the effects on different retinal cell types. The results revealed dysregulation in mitochondrial gene expression and disrupted mitochondrial morphology in ACHM retinal organoids, indicating previously unknown mitochondrial defects in the retina. Additionally, downregulation of cone genes and upregulation of Muller glia genes were observed, with no significant effects on other retinal cells.
AMERICAN JOURNAL OF PATHOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Goonho Park, Ke Xu, Leon Chea, Kyle Kim, Lance Safarta, Keon-Hyoung Song, Jian Wu, Soyoung Park, Hyejung Min, Nobuhiko Hiramatsu, Jaeseok Han, Jonathan H. Lin
Summary: Tauopathies are neurodegenerative diseases characterized by the aggregation of misfolded tau protein in the nervous system. A genetic risk factor for tauopathies, PERK, was found to be involved in regulating tau aggregation. Activating PERK prevented tau aggregation, while inhibiting PERK exacerbated tau aggregation in cell culture models. Reduced PERK signaling was found to be associated with increased tau neuropathology in patient brain tissues. These findings suggest that PERK activity protects against tau pathology and identify PERK signaling augmentation as a potential therapeutic strategy for tauopathies.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Editorial Material
Medicine, General & Internal
Christopher P. P. Long, Nicholas Coley, John Thorson, Jonathan H. H. Lin
Summary: Uveal melanoma is the most common primary ocular tumor in adults and has significant impact through lymphovascular metastasis. Monosomy 3 is a crucial prognostic indicator for metastasis. This study reports two cases of inconsistent results in monosomy 3 testing using fluorescence in situ hybridization (FISH) and chromosomal microarray analysis (CMA) in uveal melanoma specimens. These cases highlight the potential benefits of each testing modality and suggest that both methods should be pursued for a comprehensive evaluation.
Article
Neurosciences
Ragini Phansalkar, Vanessa S. Goodwill, Jeffrey J. Nirschl, Chiara De Lillo, Jihee Choi, Elizabeth Spurlock, David G. Coughlin, Donald Pizzo, Christina J. Sigurdson, Annie Hiniker, Victor E. Alvarez, Ann C. Mckee, Jonathan H. Lin
Summary: This study evaluated retinal pathology in post-mortem eyes of athletes with CTE and found novel retinal TDP43 pathology in CTE retinas, suggesting a role for p-TDP43 in producing visual deficits in patients with CTE.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Meeting Abstract
Ophthalmology
Ahmad Al Moujahed, Lance Safarta, Douglas Vollrath, Jonathan Lin
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
