Degeneration or damage of the optic nerve and the retina due to optic neuritis is a leading cause of visual loss and blindness in the United States and worldwide associated with multiple sclerosis and autoimmune damage to the CNS. The proposed multidisciplinary research project will focus on the development and characterization of a novel pharmacological intervention strategy that combines drugs to control structural and functional degeneration in autoimmune optic neuritis. Suppression of CNS inflammation, prevention of loss and damage of myelinated axons, and stimulation of regeneration and remyelination of damaged axons are the primary goals of the study. To this end, preclinical testing of the new therapeutic strategy will be performed in established models of human autoimmune optic neuritis. These experiments will determine efficacy of treatment in terminating and/or preventing autoimmune optic neuritis associated neuronal loss and preservation of visual function, and to generate data to support feasibility for and move positive findings to phase 1 or 2 clinical trials. Specifically, we will test the hypothesis that the proposed treatment strategy cn target and remedy specific phenotypes that include combinations of separate pathologies encountered during distinct stages of optic neuritis and multiple sclerosis, leading to improvement of visual impairment and functional deficits associated with the disease. The determination of neuronal viability and the acquired knowledge on associated therapeutic parameters will indicate the potential of the method to remedy autoimmune optic neuritis as the overall goal of the project. This therapy approach for autoimmune optic neuritis focuses on suppression of CNS autoimmunoreactivity, neuroprotection, axon regeneration and remyelination via different mechanisms. It has the potential to be both preventative and therapeutic and to complement existing treatment designs and rationales addressing other aspects of autoimmune optic neuritis treatment.
Multiple sclerosis affects approximately 2.5 million people worldwide and approximately 400,000 people in the United States. In multiple sclerosis, degeneration or damage of the optic nerve, the nerve that connects the eye to the brain and thereby makes vision possible, is a leading cause of loss of quality of life and productivity in th United States and worldwide. The project proposes the determination of the identity and function of novel targets for combination drug treatment that controls disease progression. As degeneration of the optic nerve affect significant and increasing portions of the U.S. population including minorities affected by disparities in health care delivery, determining causes, mechanisms of action and subsequently potential treatment strategies will contribute to improving health care, health and physical performance.
|Montgomery, Christa L; Johnson, Heather M; Johnston, Thomas P et al. (2018) Mechanisms Underlying Early-Stage Changes in Visual Performance and Retina Function After Experimental Induction of Sustained Dyslipidemia. Neurochem Res 43:1500-1510|
|Grillo, Stephanie L; Montgomery, Christa L; Johnson, Heather M et al. (2018) Quantification of Changes in Visual Function During Disease Development in a Mouse Model of Pigmentary Glaucoma. J Glaucoma 27:828-841|
|Grillo, Michael A; Grillo, Stephanie L; Gerdes, Bryan C et al. (2018) Control of Neuronal Ryanodine Receptor-Mediated Calcium Signaling by Calsenilin. Mol Neurobiol :|
|Kaja, Simon; Payne, Andrew J; Naumchuk, Yuliya et al. (2017) Quantification of Lactate Dehydrogenase for Cell Viability Testing Using Cell Lines and Primary Cultured Astrocytes. Curr Protoc Toxicol 72:2.26.1-2.26.10|
|Richter, Frank; Koulen, Peter; Kaja, Simon (2016) N-Palmitoylethanolamine Prevents the Run-down of Amplitudes in Cortical Spreading Depression Possibly Implicating Proinflammatory Cytokine Release. Sci Rep 6:23481|
|Means, John C; Gerdes, Bryan C; Kaja, Simon et al. (2016) Caspase-3-Dependent Proteolytic Cleavage of Tau Causes Neurofibrillary Tangles and Results in Cognitive Impairment During Normal Aging. Neurochem Res 41:2278-88|
|Montgomery, Christa L; Keereetaweep, Jantana; Johnson, Heather M et al. (2016) Changes in Retinal N-Acylethanolamines and their Oxylipin Derivatives During the Development of Visual Impairment in a Mouse Model for Glaucoma. Lipids 51:857-66|
|Kaja, Simon; Payne, Andrew J; Singh, Tulsi et al. (2015) An optimized lactate dehydrogenase release assay for screening of drug candidates in neuroscience. J Pharmacol Toxicol Methods 73:1-6|
|Kaja, Simon; Payne, Andrew J; Naumchuk, Yuliya et al. (2015) Plate reader-based cell viability assays for glioprotection using primary rat optic nerve head astrocytes. Exp Eye Res 138:159-66|
|Cheli, V T; Santiago González, D A; Spreuer, V et al. (2015) Voltage-gated Ca2+ entry promotes oligodendrocyte progenitor cell maturation and myelination in vitro. Exp Neurol 265:69-83|
Showing the most recent 10 out of 23 publications