Sphingolipid profile alters in retinal dystrophic P23H-1 rats and systemic FTY720 can delay retinal degeneration[S]
| Autor: | Michael T. Matthes, Matthew M. LaVail, Douglas Yasumura, Eleanor Sun, Jeremy C. Allegood, Hui Qi, Nawajes A Mandal, Charles E. Chalfant, Megan Stiles, Hunter Porter, Jeremy Tan |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Retinal degeneration FTY720 retina Drug Evaluation Preclinical Neurodegenerative Medical Biochemistry and Metabolomics Bioinformatics Eye Biochemistry Rats Sprague-Dawley chemistry.chemical_compound Endocrinology 2.1 Biological and endogenous factors Aetiology Research Articles apoptosis photoreceptors Preclinical Cell biology medicine.anatomical_structure Sphingomyelin Phosphodiesterase 5.1 Pharmaceuticals Disease Progression Development of treatments and therapeutic interventions Sphingomyelin Photoreceptor Cells Vertebrate Programmed cell death Ceramide Biochemistry & Molecular Biology hexosyl-ceramide QD415-436 Biology sphingomyelin 03 medical and health sciences P23H line 1 rats Genetic model Retinal Dystrophies medicine Animals Photoreceptor Cells ceramide fingolimod sphingomyelinase Eye Disease and Disorders of Vision Retina Sphingolipids Vertebrate Fingolimod Hydrochloride Neurosciences Retinal Cell Biology medicine.disease Sphingolipid Rats Biosynthetic Pathways 030104 developmental biology chemistry Drug Evaluation Sprague-Dawley Biochemistry and Cell Biology sense organs |
| Zdroj: | Journal of Lipid Research, Vol 57, Iss 5, Pp 818-831 (2016) Journal of lipid research, vol 57, iss 5 |
| ISSN: | 0022-2275 |
| Popis: | Retinal degeneration (RD) affects millions of people and is a major cause of ocular impairment and blindness. With a wide range of mutations and conditions leading to degeneration, targeting downstream processes is necessary for developing effective treatments. Ceramide and sphingosine-1-phosphate, a pair of bioactive sphingolipids, are involved in apoptosis and its prevention, respectively. Apoptotic cell death is a potential driver of RD, and in order to understand the mechanism of degeneration and potential treatments, we studied rhodopsin mutant RD model, P23H-1 rats. Investigating this genetic model of human RD allows us to investigate the association of sphingolipid metabolites with the degeneration of the retina in P23H-1 rats and the effects of a specific modulator of sphingolipid metabolism, FTY720. We found that P23H-1 rat retinas had altered sphingolipid profiles that, when treated with FTY720, were rebalanced closer to normal levels. FTY720-treated rats also showed protection from RD compared with their vehicle-treated littermates. Based on these data, we conclude that sphingolipid dysregulation plays a secondary role in retinal cell death, which may be common to many forms of RDs, and that the U.S. Food and Drug Administration-approved drug FTY720 or related compounds that modulate sphingolipid metabolism could potentially delay the cell death. |
| Databáze: | OpenAIRE |
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