Article
Biochemistry & Molecular Biology
Valerie Fontaine, Christine Balducci, Laurence Dinan, Elodie Monteiro, Thinhinane Boumedine, Mylene Fournie, Vincent Nguyen, Louis Guibout, Justine Clatot, Mathilde Latil, Stanislas Veillet, Jose-Alain Sahel, Rene Lafont, Pierre J. Dilda, Serge Camelo
Summary: This study introduced a novel norbixin amide conjugate, BIO203, which showed similar mode of action and protective effects as norbixin in vitro and in vivo. BIO203 exhibited better stability and pharmacokinetics, making it a potential treatment for retinal degenerative diseases such as AMD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Chae Young Shin, Sanha Lee, Hong Lan Jin, Xiang Fei, Sang Won Kang, Seung-Yong Seo, Kwang Won Jeong
Summary: In this study, we identified a compound (JS-017) that can degrade A2E and protect retinal pigment epithelial cells from damage induced by A2E and blue light. JS-017 activates autophagy to suppress the expression of inflammatory and apoptosis genes. These findings suggest the potential of JS-017 as a therapeutic agent for retinal degenerative diseases.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Tongzhou Xu, Laurie L. Molday, Robert S. Molday
Summary: N-Ret-PE, a crucial molecule in the visual cycle and visual pigment photoregeneration, can form toxic di-retinoids if not removed by ABCA4. Mutations in ABCA4 cause Stargardt disease, which is associated with the accumulation of di-retinoids and vision loss. This study investigates the factors affecting N-Ret-PE formation and identifies key amino acid residues involved in its interaction with ABCA4.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Min Jung Kim, Dong Hee Kim, Han Sub Kwak, In-Sun Yu, Min Young Um
Summary: Polyphenols in chrysanthemum extract can suppress A2E-mediated damage to RPE cells, but other substances in the extract may also play a role.
Article
Multidisciplinary Sciences
Philipp L. Mueller, Alexandru Odainic, Tim Treis, Philipp Herrmann, Adnan Tufail, Frank G. Holz, Maximilian Pfau
Summary: Through a machine-learning approach integrating imaging and patient data, accurate prediction of retinal function can be achieved. The inclusion of limited FCP data improved prediction accuracy, making it a potential surrogate marker for evaluating treatment effects or disease progression.
SCIENTIFIC REPORTS
(2021)
Review
Cell Biology
Landon J. J. Rohowetz, Peter Koulen
Summary: The eyes are immune privileged organs, making them ideal for stem cell therapy. Differentiation protocols for retinal pigment epithelium (RPE) from embryonic and induced pluripotent stem cells have been developed, allowing diseases affecting RPE to be treated with stem cell therapy. Recent advancements in diagnostic technologies have enhanced disease monitoring and response to stem cell therapy. Previous clinical trials have shown promising results, and ongoing trials aim to improve our understanding of the most effective methods of RPE-based stem cell therapy for retinal diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Ophthalmology
Jade Guenot, Yves Trotter, Paul Fricker, Marta Cherubini, Vincent Soler, Benoit R. Cottereau
Summary: This study characterized optic flow processing in patients with macular degeneration (MD) and found that selectivity to optic flow patterns is preserved in these patients.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Chae Young Shin, Mun-Hoe Lee, Hyeong-Min Kim, Hee-Chul Chung, Do-Un Kim, Jin-Hee Lee, Kwang Won Jeong
Summary: This study found that black currant extract has preventive and therapeutic effects on dry age-related macular degeneration (AMD) through its antioxidant activity and inhibition of lipofuscin accumulation in the retina.
Article
Ophthalmology
Krunoslav Stingl, Carel Hoyng, Melanie Kempf, Susanne Kohl, Ronja Jung, Giulia Righetti, Laura Kuehlewein, Lisa Pohl, Friederike Kortuem, Carina Kelbsch, Barbara Wilhelm, Tobias Peters, Katarina Stingl
Summary: Chromatic pupil campimetry (CPC) was used to map local functional degenerative changes of cones and rods in Stargardt disease (STGD1). The study found that rod function was not impaired in STGD1 patients in the peripheral visual field, while cone function was significantly reduced in the central visual field.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Review
Cell Biology
Audrey Voisin, Amaury Penaguin, Afsaneh Gaillard, Nicolas Leveziel
Summary: Alterations in the outer retina can lead to diseases such as age-related macular degeneration or retinitis pigmentosa, which are characterized by reduced visual acuity and eventual blindness. Despite extensive research, there is currently no curative treatment available for retinal disorders. However, several therapeutic approaches, including cell-based replacement and gene therapies, are being developed. This review provides an overview of the progress in stem cell therapies for retinal diseases, encompassing pre-clinical studies to clinical trials.
NEURAL REGENERATION RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Luigi Donato, Concetta Scimone, Simona Alibrandi, Sergio Zaccaria Scalinci, Carmela Rinaldi, Rosalia D'Angelo, Antonina Sidoti
Summary: This study demonstrates for the first time the dynamic RNA editome profiles in human retinal pigment epithelium cells, shedding more light on new mechanisms underlying retinal degeneration.
Review
Biochemistry & Molecular Biology
Elena Piotter, Michelle E. McClements, Robert E. MacLaren
Summary: Despite being a common cause of inherited blindness in children, Stargardt disease has not achieved the same clinical trial success as other inherited retinal diseases. The early onset and continual progression of the disease have led to the development of various treatment strategies, including small molecules, gene supplementation, and cell replacement. The advancement of CRISPR-based molecular tools is also expected to contribute to future therapies for Stargardt disease.
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
Biology
Dan Zhang, Doina M. Mihai, Ilyas Washington
Summary: The study found that the vitamin A byproduct A2E alone is sufficient to cause retinal damage and functional decline, potentially being the root cause of retinal diseases. Delaying the formation of vitamin A byproducts could help prevent retinal diseases.
Article
Ophthalmology
Ankita Kotnala, Srinivasan Senthilkumari, Gong Wu, Thomas G. Stewart, Christine A. Curcio, Nabanita Halder, Sundararajan Baskar Singh, Atul Kumar, Thirumurthy Velpandian
Summary: The study found that levels of all assayed compounds were significantly higher in the periphery than in the macula in eyes of different ages, indicating biological differences between these regions. A2E, A2DHPE, and MFA2E increased with age, while A2GPE remained unaffected.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
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)
Article
Clinical Neurology
Nancy J. Newman, Patrick Yu-Wai-Man, Prem S. Subramanian, Mark L. Moster, An-Guor Wang, Sean P. Donahue, Bart P. Leroy, Valerio Carelli, Valerie Biousse, Catherine Vignal-Clermont, Robert C. Sergott, Alfredo A. Sadun, Gema Rebolleda Fernandez, Bart K. Chwalisz, Rudrani Banik, Fabienne Bazin, Michel Roux, Eric D. Cox, Magali Taiel, Jose-Alain Sahel
Summary: Leber hereditary optic neuropathy (LHON) is a mitochondrial blindness caused by the m.11778G>A mutation. The REFLECT phase 3 study investigated the efficacy and safety of lenadogene nolparvovec gene therapy in LHON patients. It showed improvement in visual acuity, with better results in patients who received bilateral treatment. The trial demonstrated a favorable benefit/risk profile for bilateral injections compared to unilateral injections.
Editorial Material
Medicine, Research & Experimental
Boris Rosin, Jose-Alain Sahel
Summary: Ocular and specifically retinal toxicities caused by systemic medications are common and cover various disease modalities. Established follow-up protocols are in place for many of these drugs to ensure timely detection and cessation of therapy. The recent study by Kong et al (2023) in EMBO Molecular Medicine investigated the retinal toxicity induced by deferoxamine (DFO) using both in vivo and in vitro techniques. Their findings suggest a potential protective role for alpha-ketoglutarate (AKG) supplementation against DFO toxicity.
EMBO MOLECULAR MEDICINE
(2023)
Article
Multidisciplinary Sciences
Amrish Selvam, Sumit Randhir Singh, Supriya Arora, Manan Patel, Arnim Kuchhal, Stavan Shah, Joshua Ong, Mohammed Abdul Rasheed, Shanmukh Reddy Manne, Mohammed Nasar Ibrahim, Jose-Alain Sahel, Kiran Kumar Vupparaboina, Jay Chhablani
Summary: We conducted an automated analysis of pigment epithelial detachments (PEDs) in neovascular age related macular degeneration (nAMD) to estimate the areas of serous, neovascular, and fibrous tissues within the PEDs. By manually segmenting the PEDs and filtering the pixels using 2D kernels, we were able to classify them as serous, neovascular, or fibrous. Using specific PED composition indices, we calculated the relative areas of each tissue type within the PEDs. The accuracy of segmentation and classification was graded, and overall repeatability and reproducibility were high.
SCIENTIFIC REPORTS
(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
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)
Article
Biochemistry & Molecular Biology
Valerie Fontaine, Christine Balducci, Laurence Dinan, Elodie Monteiro, Thinhinane Boumedine, Mylene Fournie, Vincent Nguyen, Louis Guibout, Justine Clatot, Mathilde Latil, Stanislas Veillet, Jose-Alain Sahel, Rene Lafont, Pierre J. Dilda, Serge Camelo
Summary: This study introduced a novel norbixin amide conjugate, BIO203, which showed similar mode of action and protective effects as norbixin in vitro and in vivo. BIO203 exhibited better stability and pharmacokinetics, making it a potential treatment for retinal degenerative diseases such as AMD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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)
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)
Meeting Abstract
Ophthalmology
Alice Le Meur, Daniel C. Chung, Lea Thiebault, Pierre-Axel Vinot, Berthe Pom, Thierry D. Leveillard, Saddek Mohand-Said, Jose Alain Sahel, Isabelle S. Audo
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
