title: PSA modification of NCAM supports the survival of injured retinal ganglion cells in adulthood.
abstract: Neural cell adhesion molecule (NCAM) is known as the cell surface glycoprotein, and it belongs to the immunoglobulin superfamily of adhesion molecules. Polysialic acid (PSA) is a carbohydrate attached to NCAM via either of two specific sialyltransferases: ST8SiaII and ST8SiaIV. Polysialylated neural cell adhesion molecule (PSA-NCAM) mediates cell interactions, plays a role in axon growth, migration, synaptic plasticity during development and cell regeneration. Some evidence has shown that PSA-NCAM supports the survival of neurons. It was demonstrated that PSA-NCAM is present in abundance in the retina during development and in adulthood. The aim of this study was to investigate whether PSA-NCAM promotes retinal ganglion cell (RGC) survival in transgenic mice with deficiencies in sialyltransferases or NCAM or after the administration of endoneuraminidase (Endo-N). RGC injury was induced by intravitreal administration of kainic acid (KA). These studies showed that injection of Endo-N after 14 days enhances the toxicity of KA to RGCs in wild-type (WT) mice by 18%. In contrast, in knockout mice (ST8SiaII-/-, ST8SiaIV-/-, NCAM-/-), survival of RGCs after KA injury did not change. Deficiencies of either ST8SiaII or ST8SiaIV did not influence the level of PSA-NCAM in the adult retina, however, in neonatal animals, decreased levels of PSA-NCAM were observed. In knockout ST8SiaII-/- adults, a reduced number of RGCs was detected, whereas in contrast, increased numbers of RGCs were noted in NCAM-/- mice. In conclusion, these data demonstrate that PSA-NCAM supports the survival of injured RGCs in adulthood. However, the role of PSA-NCAM in the adult retina requires further clarification.
authors: Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia.
authors: Natalia
authors: N
authors: Lobanovskaya
authors: Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia.
authors: Tamara
authors: T
authors: Zharkovsky
authors: Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia.
authors: Külli
authors: K
authors: Jaako
authors: Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia.
authors: Monika
authors: M
authors: Jürgenson
authors: Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia.
authors: Anu
authors: A
authors: Aonurm-Helm
authors: Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia. Electronic address: aleksander.zarkovski@ut.ee.
authors: Alexander
authors: A
authors: Zharkovsky
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002470:Cell Survival / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000633:toxicity; D007608:Kainic Acid / Q000633:toxicity; D051379:Mice; D018345:Mice, Knockout; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism*; D012794:Sialic Acids / Q000378:metabolism*; D012799:Sialyltransferases / Q000172:deficiency / Q000235:genetics; D013997:Time Factors
chemical_list: D005904:Glial Fibrillary Acidic Protein; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule; C526452:ST8SiaII protein, mouse; D012799:Sialyltransferases; C525848:ST8SiaIV protein, mouse; D006026:Glycoside Hydrolases; C090534:endo-alpha-sialidase; D007608:Kainic Acid
keywords: Neuraminidase; PSA-NCAM; Retinal ganglion cell; Sialyltransferase