Purpose: Semaphorin 3A (Sema-3A) is a secreted protein that deflects axons from inappropriate regions and induces neuronal cell death. Intravitreal application of polyclonal antibodies against Sema-3A prevents loss of retinal ganglion cells ensuing from axotomy of optic nerves. This suggested a therapeutic approach for neuroprotection via inhibition of the Sema-3A pathway.
Methods: To develop potent and specific Sema-3A antagonists, we isolated monoclonal anti-Sema-3A antibodies from a human antibody phage display library and optimized low-molecular weight Sema-3A signaling inhibitors. The best inhibitors were identified using in vitro scratch assays and semiquantitative repulsion assays.
Results: A therapeutic approach for neuroprotection must have a long duration of action. Therefore, antibodies and low-molecular weight inhibitors were formulated in extruded implants to allow controlled and prolonged release. Following release from the implants, Sema-3A inhibitors antagonized Sema-3A effects in scratch and repulsion assays and protected retinal ganglion cells in animal models of optic nerve injury, retinal ischemia, and glaucoma.
Conclusions And Translational Relevance: Collectively, our findings indicate that the identified Sema-3A inhibitors should be further evaluated as therapeutic candidates for the treatment of Sema-3A-driven central nervous system degenerative processes.
Departamento de Neurociencias Integrativas y Computacionales, Lab. Neurobiología Comparada, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Avenida. Italia 3318, 11600, Montevideo, Uruguay; Laboratorio de Neurociencias, Facultad de Ciencias, Universidad de la República, Iguá 4225, 11400, Montevideo, Uruguay. Electronic address:
Fish with unique life cycles offer valuable insights into retinal plasticity, revealing mechanisms of environmental adaptation, cell proliferation, and thus, potentially regeneration. The variability of the environmental factors to which Austrolebias annual fishes are exposed has acted as a strong selective pressure shaping traits such as nervous system plasticity. This has contributed to adaptation to their extreme conditions including the decreased luminosity as ponds dry out.
Background: Retinal ganglion cell (RGC) death caused by acute ocular hypertension is an important characteristic of acute glaucoma. Receptor-interacting protein kinase 3 (RIPK3) that mediates necroptosis is a potential therapeutic target for RGC death. However, the current understanding of the targeting agents and mechanisms of RIPK3 in the treatment of glaucoma remains limited.
Background: Bipolar disorder (BD) is a psychiatric condition with significant health implications due to its comorbidities, premature mortality, and functional impairments. Despite extensive research on treatment and rehabilitation, gaps remain in diagnosis and monitoring. Therefore, there is a need for biomarkers to identify individuals at risk for disease progression or excacerbation.
Barcelona Clinic Schizophrenia Unit, Institute of Neurosciences, Hospital Clinic, Barcelona, Spain; Institut d'Investigacions Mèdiques August Pi i Sunyer (IDIBAPS), Fundació Clínic, Barcelona, Spain; Biomedical Research Networking Centre Consortium on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain. Electronic address:
Emerging evidence suggests that retinal structural alterations are present in schizophrenia spectrum disorders (SSD), potentially reflecting broader neurodevelopmental and neurodegenerative processes. This cross-sectional study investigates retinal thickness and its clinical correlations in a sample of early-course SSD patients compared to healthy controls (HCs). One hundred-two eyes from 26 SSD cases and 25 age- and sex-matched HCs were included.
Background: Dementia poses a significant burden on healthcare systems. Early identification of individuals at risk for cognitive decline is crucial. The retina, an extension of the central nervous system, reflects neurodegenerative changes.
