Article
Ophthalmology
Marina Yasvoina, Qian Yang, Sasha M. Woods, Tjebo Heeren, Grant M. Comer, Catherine A. Egan, Marcus Fruttiger
Summary: This study found that RPE cells invading the retina in retinal degenerative diseases undergo dedifferentiation and can be pigmented or unpigmented. As a result, the number of these cells may be underestimated through funduscopy.
BRITISH JOURNAL OF OPHTHALMOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Izarbe Aisa-Marin, Rocio Garcia-Arroyo, Serena Mirra, Gemma Marfany
Summary: Alternative splicing of mRNA is crucial for regulating and increasing the diversity of transcriptome and proteome. The retina, as an extension of the central nervous system, illustrates the high diversity of neural transcripts with complex splicing programs. Modulation of alternative splicing in the retina is essential for designing novel therapeutic approaches for retinal dystrophies and enabling precision medicine for specific mutations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biotechnology & Applied Microbiology
Karla Alejandra Ruiz-Ceja, Dalila Capasso, Michele Pinelli, Eugenio Del Prete, Diego Carrella, Diego di Bernardo, Sandro Banfi
Summary: This study explores the transcript composition of inherited retinal disease genes in the human retina through a meta-analysis of publicly available RNA-seq datasets. It identifies many previously unreported transcripts and examines their potential impact on the protein level. The findings contribute to understanding the missing heritability in inherited retinal diseases.
Article
Neurosciences
Una Greferath, Mario Huynh, Andrew Ian Jobling, Kirstan Anne Vessey, Gene Venables, Denver Surrao, Helen Christine O'Neill, Ioannis J. Limnios, Erica Lucy Fletcher
Summary: Retinitis pigmentosa is a group of inherited retinal degenerations characterized by gradual loss of photoreceptors, ultimately leading to irreversible vision loss. This study focused on analyzing the changes in glial, microglial, and photoreceptor cells in different retinal locations in RCS rats, revealing significant differences in photoreceptor loss between the dorsal and ventral retina. The findings suggest that breakdown of the outer limiting membrane may play a role in exacerbating photoreceptor loss in the ventral retina, highlighting the value of using the RCS rat model for sectorial retinitis pigmentosa.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Cell & Tissue Engineering
Hani Jieun Kim, Michelle O'Hara-Wright, Daniel Kim, To Ha Loi, Benjamin Y. Lim, Robyn V. Jamieson, Anai Gonzalez-Cordero, Pengyi Yang
Summary: Characterizing cell identities in the human retina is important for studying its development and disease. This study evaluated the fidelity of retinal organoids in mimicking the human eye by systematically assessing the molecular and cellular characteristics of both the organoids and human eye tissues. The results provided new biomarkers for major retinal cell types and insights into the maturation process, allowing for comprehensive benchmarking of current protocols for retinal organoid generation.
Article
Cell Biology
Ashley Y. Gao, Patrick A. Link, Sophie J. Bakri, Andrew J. Haak
Summary: This study elucidates the role of dopamine receptor signaling in regulating the fibrotic activation of retinal pigmented epithelial (RPE) cells. It shows that DRD2 and DRD5 are the dominant dopamine receptors expressed in ARPE-19 cells and that TGF-beta stimulation enhances the autocrine release of dopamine, exacerbating fibrotic activation. Treatment with D2 dopamine receptor antagonists or D5 dopamine receptor agonists effectively inhibits profibrotic gene expression, migration, proliferation, and fibronectin deposition, providing potential mechanisms for treating retinal fibrosis including proliferative vitreoretinopathy (PVR).
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Mariana I. Holubiec, Juan I. Romero, Claudia Urbainsky, Manuela Gellert, Pablo Galeano, Francisco Capani, Christopher Horst Lillig, Eva-Maria Hanschmann
Summary: Nucleoredoxin (Nrx), a member of the Thioredoxin protein family, plays a crucial role in redox-mediated signal transduction. It regulates cell differentiation and is essential for maintaining cell morphology. Nrx is involved in increasing the number of glial cells and replenishing neurons lost due to hypoxic insult. These regulatory changes are related to VEGF but not the Wnt/beta-catenin pathway.
Article
Neurosciences
Wei Wei, Piaopiao Hu, Mengqi Qin, Guiping Chen, Feifei Wang, Shengrui Yao, Ming Jin, Zhi Xie, Xu Zhang
Summary: SIRT4 is highly expressed in retinal Muller glial cells and is relevant to the expression of GS. SIRT4 does not appear to be essential in retinal development, but resveratrol, as an activator of SIRT4, can upregulate GS protein expression and protect the retina.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Biology
Joaquin Letelier, Lorena Buono, Maria Almuedo-Castillo, Jingjing Zang, Constanza Mounieres, Sergio Gonzalez-Diaz, Rocio Polvillo, Estefania Sanabria-Reinoso, Jorge Corbacho, Ana Sousa-Ortega, Ruth Diez del Corral, Stephan C. F. Neuhauss, Juan R. Martinez-Morales
Summary: Genetic studies have shown that Vsx genes play a dual role in retina development, being involved in progenitor specification and determination of bipolar cell fate. However, the extent to which Vsx functions are conserved across vertebrates is still unclear. In this study, Vsx1 and Vsx2 were knocked out in zebrafish embryos using CRISPR/Cas9, resulting in severe visual impairment and depletion of bipolar cells. Surprisingly, the neural retina was properly specified and maintained in mutant embryos. The findings suggest that genetic redundancy is an important mechanism for maintaining the integrity of the retinal specification network.
Article
Biochemistry & Molecular Biology
Mi-Jin An, Hyun-Min Lee, Chul-Hong Kim, Geun-Seup Shin, Ah-Ra Jo, Ji-Young Kim, Mi Jin Kim, Jinho Kim, Jinhong Park, Yujeong Hwangbo, Jeongkyu Kim, Jung-Woong Kim
Summary: This study identifies JNK1 as a protein that can phosphorylate the OTX2 transcription factor through protein-protein interaction.
Article
Biology
Peng Shang, Nadezda Stepicheva, Kenneth Teel, Austin McCauley, Christopher Scott Fitting, Stacey Hose, Rhonda Grebe, Meysam Yazdankhah, Sayan Ghosh, Haitao Liu, Anastasia Strizhakova, Joseph Weiss, Imran A. Bhutto, Gerard A. Lutty, Ashwath Jayagopal, Jiang Qian, Jose-Alain Sahel, J. Samuel Zigler, James T. Handa, Yuri Sergeev, Raju V. S. Rajala, Simon Watkins, Debasish Sinha
Summary: The study highlights the crucial role of beta A3/A1-crystallin in the retinal pigmented epithelium, with its deficiency causing EGFR endocytosis defects and actin network disruption leading to polarity disruption and degeneration through the PITP beta/PLC signaling pathway.
COMMUNICATIONS BIOLOGY
(2021)
Article
Medicine, Research & Experimental
Lingjun Zhang, Nozha Borjini, Yu Lun, Sweta Parab, Gospel Asonye, Rupesh Singh, Brent A. Bell, Vera L. Bonilha, Andrei Ivanov, David A. Fox, Rachel Caspi, Feng Lin
Summary: CDCP1, highly expressed on the surface of cancer cells, was found to be present on retinal pigment epithelial (RPE) cells. It interacts with CD6 on T cells, inducing cytoskeleton remodeling and focal adhesion disruption in RPE cells, leading to the development of autoimmune uveitis.
Article
Ophthalmology
Sugao Miyagi, Anri Nishinaka, Takumi Yamamoto, Wataru Otsu, Shinsuke Nakamura, Masamitsu Shimazawa, Takashi Kitaoka, Hideaki Hara
Summary: A pigmented murine RVO model was established in this study, reproducing characteristic fundus appearances similar to human RVO findings and exhibiting retinal edema. Real-time PCR analysis showed an increase in VEGF mRNA level in the induced retinal RVO, and intravitreal injection of anti-VEGF antibody reduced retinal edema. These results were consistent with human clinical knowledge and suggested the model as a useful tool for research on new therapeutic approaches.
EXPERIMENTAL EYE RESEARCH
(2021)
Article
Medicine, Research & Experimental
Kevin T. Eade, Brendan Robert E. Ansell, Sarah Giles, Regis Fallon, Sarah Harkins-Perry, Takayuki Nagasaki, Simone Tzaridis, Martina Wallace, Elizabeth A. Mills, Samaneh Farashi, Alec Johnson, Lydia Sauer, Barbara Hart, M. Elena Diaz-Rubio, Melanie Bahlo, Christian Metallo, Rando Allikmets, Marin L. Gantner, Paul S. Bernstein, Martin Friedlander
Summary: Patient-derived iPSCs are a powerful tool for studying disease mechanisms, with MacTel iRPE cells showing reduced serine levels and dysregulation of central carbon metabolism. Mitochondrial dysfunction in these cells may represent an alternative disease mechanism beyond the known serine/sphingolipid pathway.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Cell Biology
Yuxiao Zeng, Minghui Li, Ting Zou, Xi Chen, Qiyou Li, Yijian Li, Lingling Ge, Siyu Chen, Haiwei Xu
Summary: The study demonstrated that PM2.5 exposure affected the formation of neural retina derived from hEROs, leading to reduced proliferation and increased apoptosis. Transcriptome analysis showed that PM2.5 treatment was linked to MAPK and PI3K/Akt pathways, and reduced the level of FGFs, particularly FGF8 and FGF10, suggesting potential inhibition of proliferation and increase of apoptosis during early human retinal development.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Urvi Gupta, Sayan Ghosh, Callen T. Wallace, Peng Shang, Ying Xin, Archana Padmanabhan Nair, Meysam Yazdankhah, Anastasia Strizhakova, Mark A. Ross, Haitao Liu, Stacey Hose, Nadezda A. Stepicheva, Olivia Chowdhury, Mihir Nemani, Vishnu Maddipatla, Rhonda Grebe, Manjula Das, Kira L. Lathrop, Jose-Alain Sahel, J. Samuel Zigler, Jiang Qian, Arkasubhra Ghosh, Yuri Sergeev, James T. Handa, Claudette M. St Croix, Debasish Sinha
Summary: In dry age-related macular degeneration, increased LCN2 levels lead to pathological changes in retinal pigmented epithelial cells, which are known to drive dry AMD pathology. By regulating autophagy and ferroptosis activities, LCN2 is involved in the development of AMD and provides a potential therapeutic strategy.
Editorial Material
Ophthalmology
Gabriel Hallali, Sjoukje E. Loudon, Anthony G. Robson, Saddek Mohand-Said, Xavier Zanlonghi, Jose-Alain Sahel, Antony T. Moore, Isabelle Audo
ACTA OPHTHALMOLOGICA
(2023)
Letter
Ophthalmology
Mridula Dilip, Zachary Koretz, Manuel A. Paez-Escamilla, Emily Hughes, Jose-Alain Sahel, Ian Conner, Marie-Helene Errera
Summary: This case report highlights a unique late complication of the Xen gel stent, namely stent-related endophthalmitis, which was preceded by flattening of the bleb. The use of B-scan and anterior chamber tap helped in the diagnosis, and intravitreal antibiotics proved effective in treating the patient.
OCULAR IMMUNOLOGY AND INFLAMMATION
(2023)
Article
Ophthalmology
Catherine Vignal-Clermont, Patrick Yu-Wai-Man, Nancy J. Newman, Valerio Carelli, Mark L. Moster, Valerie Biousse, Prem S. Subramanian, An-Guor Wang, Sean P. Donahue, Bart P. Leroy, Alfredo A. Sadun, Thomas Klopstock, Robert C. Sergott, Gema Rebolleda Fernandez, Bart K. Chwalisz, Rudrani Banik, Magali Taiel, Michel Roux, Jose-Alain Sahel
Summary: This study evaluated the safety profile of Lenadogene nolparvovec in patients with Leber hereditary optic neuropathy. A total of 189 patients received intravitreal injections of a recombinant adeno-associated virus 2 vector encoding the ND4 gene. The results showed that Lenadogene nolparvovec had a good overall safety profile with excellent systemic tolerability, and there were no serious treatment-related adverse events.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2023)
Editorial Material
Cell Biology
Mariangela Corsi, Celine Jaillard, Thierry Leveillard
NEURAL REGENERATION RESEARCH
(2023)
Review
Ophthalmology
Christina Zeitz, Jerome E. Roger, Isabelle Audo, Christelle Michiels, Nuria Sanchez-Farias, Juliette Varin, Helen Frederiksen, Baptiste Wilmet, Jacques Callebert, Marie-Laure Gimenez, Nassima Bouzidi, Frederic Blond, Xavier Guilllonneau, Stephane Fouquet, Thierry Leveillard, Vasily Smirnov, Ajoy Vincent, Elise Heon, Jose-Alain Sahela, Barbara Kloeckener-Gruissemi, Florian Sennlaub, Catherine W. Morgansj, Robert M. Duvoisinj, Andrei V. Tkatchenko, Serge Picaud
Summary: Myopia is a common eye disorder caused by genetic and environmental factors. High myopia is often associated with rare inherited retinal disorders. Genes involved in myopia are related to various biological processes, including eye development, matrix organization, visual perception, circadian rhythms, and retinal signaling. Animal models mimicking myopia can help identify candidate genes implicated in human myopia. Complete congenital stationary night blindness represents an interesting model for studying myopia and retinal signaling defects. Transcriptome analysis in mouse models of cCSNB identified new candidate genes for myopia. Integration of transcriptomic data and genome-wide association studies provides insights into the potential mechanisms underlying myopia development in cCSNB subjects. These findings have implications for the development of pharmacological therapies for myopia.
PROGRESS IN RETINAL AND EYE RESEARCH
(2023)
Article
Ophthalmology
Valerio Carelli, Nancy J. Newman, Patrick Yu-Wai-Man, Valerie Biousse, Mark L. Moster, Prem S. Subramanian, Catherine Vignal-Clermont, An-Guor Wang, Sean P. Donahue, Bart P. Leroy, Robert C. Sergott, Thomas Klopstock, Alfredo A. Sadun, Gema Rebolleda Fernandez, Bart K. Chwalisz, Rudrani Banik, Jean Francois Girmens, Chiara La Morgia, Adam A. DeBusk, Neringa Jurkute, Claudia Priglinger, Rustum Karanjia, Constant Josse, Julie Salzmann, Francois Montestruc, Michel Roux, Magali Taiel, Jose-Alain Sahel, The Lhon Study Group
Summary: Lenadogene nolparvovec is a promising gene therapy for LHON patients with MT-ND4 mutation, showing sustained visual acuity improvement compared to natural history. Incorporation of data from the latest trial REFLECT indicates that bilateral injection may offer added benefits over unilateral injection.
OPHTHALMOLOGY AND THERAPY
(2023)
Article
Engineering, Biomedical
Carter J. Teal, Margaret T. Ho, Lia Huo, Hidekiyo Harada, Laura C. Bahlmann, Thierry Leveillard, Philippe P. Monnier, Arun Ramachandran, Molly S. Shoichet
Summary: Retinitis pigmentosa (RP) is a genetic disease that leads to degeneration of rod photoreceptor cells, resulting in impaired vision and blindness. We developed an affinity-controlled release strategy using a modified blend of hyaluronan and methylcellulose (HAMC) to deliver the protein RdCVFL to the retina. Our system demonstrated sustained release of RdCVFL and enhanced cone cell viability, potentially improving the treatment of retinal degenerative diseases.
ACTA BIOMATERIALIA
(2023)
Article
Ophthalmology
Jacque L. Duncan, Peiyao Cheng, Maureen G. Maguire, Allison A. Ayala, David G. Birch, Janet K. Cheetham, Todd A. Durham, Abigail T. Fahim, Carel B. Hoyng, Hiroshi Ishikawa, Michel Michaelides, Mark E. Pennesi, Jose-Alain Sahel, Katarina Stingl, Christina Y. Weng
Summary: A prospective observational study was conducted on 102 patients with USH2A-related retinal degeneration over a period of two years. It was found that quantitative measures of static perimetry significantly declined during this time. The greatest changes were observed in the full field and peripheral vision, while the central vision showed the least change.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2023)
Review
Clinical Neurology
Eleni Stefanou, Nikolaos Karvelas, Samuel Bennett, Christo Kole
Summary: The risk of cerebrovascular manifestations is significantly increased within the first 6 months of SARS-CoV-2 infection. The incidence of acute ischemic stroke and hemorrhagic stroke during acute SARS-CoV-2 patients is estimated at 0.9% to 4.6% and 0.5%-0.9% respectively, and were associated with increased mortality.
CURRENT TREATMENT OPTIONS IN NEUROLOGY
(2023)
Article
Immunology
Sebastien Augustin, Marion Lam, Sophie Lavalette, Anna Verschueren, Frederic Blond, Valerie Forster, Lauriane Przegralek, Zhiguo He, Daniel Lewandowski, Alexis-Pierre Bemelmans, Serge Picaud, Jose-Alain Sahel, Thibaud Mathis, Michel Paques, Gilles Thuret, Xavier Guillonneau, Cecile Delarasse, Florian Sennlaub
Summary: Through studying human donor tissue, researchers have discovered that the majority of cells containing retinal melanosome/melanolipofuscin are actually melanophages, rather than migrating retinal pigment epithelial cells. They have also identified the mechanism by which melanophages form, involving the transfer of melanosomes from the retinal pigment epithelial cells to subretinal mononuclear phagocytes when the CD47 signal is blocked. These melanophages result in the formation of hyperreflective foci and are associated with RPE dysmorphia similar to intermediate AMD. Additionally, the study found that CD47 expression in human RPE decreases with age and in AMD, suggesting that boosting CD47 expression may protect RPE cells and delay AMD progression.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Biotechnology & Applied Microbiology
Benjamin Noel, France Denoeud, Alice Rouan, Carol Buitrago-Lopez, Laura Capasso, Julie Poulain, Emilie Boissin, Melanie Pousse, Corinne Da Silva, Arnaud Couloux, Eric Armstrong, Quentin Carradec, Corinne Cruaud, Karine Labadie, Julie Le-Hoang, Sylvie Tambutte, Valerie Barbe, Clementine Moulin, Guillaume Bourdin, Guillaume Iwankow, Sarah Romac, Sylvain Agostini, Bernard Banaigs, Emmanuel Boss, Chris Bowler, Colomban de Vargas, Eric Douville, J. Michel Flores, Didier Forcioli, Paola Furla, Pierre E. Galand, Fabien Lombard, Stephane Pesant, Stephanie Reynaud, Matthew B. Sullivan, Shinichi Sunagawa, Olivier P. Thomas, Romain Trouble, Rebecca Vega Thurber, Denis Allemand, Serge Planes, Eric Gilson, Didier Zoccola, Patrick Wincker, Christian R. Voolstra, Jean-Marc Aury
Summary: In the Tara Pacific expedition, we assembled two coral genomes, Porites lobata and Pocillopora cf. effusa, with greatly improved contiguity. We annotated their gene catalog and found a relatively high number of genes, 43,000 and 32,000, respectively. These duplicated genes are mainly related to the immune system and disease resistance, providing insights into the stress resilience of reef-building corals.
Meeting Abstract
Pharmacology & Pharmacy
Lucie Churet, Melanie Marie, Hanen Khabou, Deniz Dalkara, Jose-Alain Sahel, Thierry Leveillard, Florence Lorget
INTERNATIONAL JOURNAL OF TOXICOLOGY
(2023)
Meeting Abstract
Pharmacology & Pharmacy
Melanie Marie, Lucie Churet, Gregg Prawdzik, Pierre-Axel Vinot, Thierry Leveillard, Jose-Alain Sahel, Myriam Marussig, Florence Lorget
INTERNATIONAL JOURNAL OF TOXICOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Baptiste Wilmet, Jacques Callebert, Robert Duvoisin, Ruben Goulet, Christophe Tourain, Christelle Michiels, Helen Frederiksen, Frank Schaeffel, Olivier Marre, Jose Alain Sahel, Isabelle Audo, Serge Picaud, Christina Zeitz
Summary: Mutations in the GPR179 gene are a common cause of autosomal recessive complete congenital stationary night blindness (cCSNB). This study found that the absence of Gpr179 and the impaired ON-pathway may lead to myopic features in a mouse model of cCSNB. The altered dopaminergic system in Gpr179(-/-) mice is associated with an increased susceptibility to lens-induced myopia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
