51. Sphingolipids as critical players in retinal physiology and pathology
- Author
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Nawajes A Mandal, Sandip K. Basu, Richard C. Grambergs, Bano Qaladize, M. Victoria Simón, and Nora P. Rotstein
- Subjects
0301 basic medicine ,RETINITIS PIGMENTOSA ,genetic structures ,DR, diabetic retinopathy ,DHCer, dihydroceramide ,Physiology ,030204 cardiovascular system & hematology ,Biochemistry ,AH, aqueous humor ,purl.org/becyt/ford/1 [https] ,ASAH, N-acyl-sphingosine amidohydrolase ,S1PR, S1P receptor ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Sph, sphingosine ,AMD, age-related macular degeneration ,GCS, glucosylceramide synthase ,ceramide-1-phosphate ,CDase, ceramidase ,music.instrument ,C1P, ceramide 1-phosphate ,AGE-RELATED MACULAR DEGENERATION ,PARP-1, poly-ADP ribose polymerase 1 ,purl.org/becyt/ford/3.1 [https] ,SphK, sphingosine kinase ,SPT, serine palmitoyl transferase ,VEGF, vascular endothelial growth factor ,medicine.anatomical_structure ,OAG, open-angle glaucoma ,BDNF, brain-derived neurotrophic factor ,SMS, SM synthase ,purl.org/becyt/ford/3 [https] ,lipids (amino acids, peptides, and proteins) ,CerK, ceramide kinase ,Thematic Review Series: Seeing 2020: Lipids and Lipid-Soluble Molecules in the Eye ,Ceramide ,RPE, retinal pigment epithelium ,GlcCer, glucosylceramide ,NGF, nerve growth factor ,HexCer, hexosylceramide ,Cer, ceramide ,PDR, proliferative diabetic retinopathy ,QD415-436 ,GalCer, galactosylceramide ,CFH, complement factor H ,VMD, vitelliform macular dystrophy ,03 medical and health sciences ,Lactosylceramide ,nSMase, neutral sphingomyelinase ,retinitis pigmentosa ,BEST1, bestrophin-1 ,PKC, protein kinase C ,Retinitis pigmentosa ,medicine ,ceramide ,Sphingosine-1-phosphate ,purl.org/becyt/ford/1.6 [https] ,RP, retinitis pigmentosa ,music ,age-related macular degeneration ,photoreceptor degeneration ,Sphingolipids ,Retina ,Retinal pigment epithelium ,SPHINGOSINE-1-PHOSPHATE ,hBest1, human bestrophin-1 ,CERAMIDE ,aSMase, acid SMase ,business.industry ,EAU, experimental autoimmune uveoretinitis ,Thematic Review Series ,Retinal ,Cell Biology ,medicine.disease ,PHOTORECEPTOR DEGENERATION ,IOP, intraocular pressure ,Sphingolipid ,CERAMIDE-1-PHOSPHATE ,eye diseases ,030104 developmental biology ,GA, geographic atrophy ,chemistry ,CerS, ceramide synthase ,sphingosine-1-phosphate ,LacCer, lactosylceramide ,ADIPOR1, adiponectin receptor 1 ,sense organs ,Mac Tel, macular telangiectasia ,business ,POAG, primary open-angle glaucoma ,CERKL, ceramide kinase-like - Abstract
Sphingolipids have emerged as bioactive lipids involved in the regulation of many physiological and pathological processes. In the retina, they have been established toparticipate in numerousprocesses, suchas neuronal survival and death, proliferation and migration of neuronal and vascular cells, inflammation, and neovascularization. Dysregulation of sphingolipids is therefore crucial in the onset and progression of retinal diseases. This review examines the involvement of sphingolipids in retinal physiology and diseases. Ceramide (Cer) has emerged as a common mediator of inflammation and death of neuronal and retinal pigment epithelium cells in animal models of retinopathies such as glaucoma, age-related macular degeneration (AMD), and retinitis pigmentosa. Sphingosine- 1-phosphate (S1P) has opposite roles, preventing photoreceptor and ganglion cell degeneration but also promoting inflammation, fibrosis, and neovascularization in AMD, glaucoma, and pro-fibrotic disorders. Alterations in Cer, S1P, and ceramide 1- phosphate may also contribute to uveitis. Notably, use of inhibitors that either prevent Cer increase or modulate S1P signaling, such as Myriocin, desipramine, and Fingolimod (FTY720), preserves neuronal viability and retinal function. These findings underscore the relevance of alterations in the sphingolipid metabolic network in the etiology of multiple retinopathies and highlight the potential of modulating their metabolism for the design of novel therapeutic approaches. Fil: Simon, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina Fil: Basu, Sandip K.. University of Tennessee; Estados Unidos Fil: Qaladize, Bano. University of Tennessee; Estados Unidos Fil: Grambergs, Richards. University of Tennessee; Estados Unidos Fil: Rotstein, Nora Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina Fil: Mandal, Nawajes .A.. University of Tennessee; Estados Unidos
- Published
- 2021