HIV-Tat-mediated Bcl-XL delivery protects retinal ganglion cells during experimental autoimmune optic neuritis.
In multiple sclerosis (MS), post-mortem studies of human brain tissue as well as data from animal models have shown that apoptosis of neurons occurs to a significant extent during this disease. As neurodegeneration in MS correlates with permanent neurological deficits in patients, understanding the mechanisms would be an important pre-condition for designing appropriate neuroprotective therapies. Myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis often affects the optic nerve and leads to consecutive apoptosis of retinal ganglion cells (RGCs), the neurons that form its axons. In this study, we fused Bcl-XL to the protein transduction domain of the HIV-transactivator of transcription. Thereby, this anti-apoptotic member of the Bcl-2 family was delivered into RGCs of rats with electrophysiologically diagnosed optic neuritis. Transduction of Bcl-XL in our study led to significant rescue of RGCs indicating the relevance of this pathway for neuronal survival under autoimmune inflammatory conditions.
Diem
Ricarda
R
Neurologische Universitätsklinik, Robert-Koch-Str. 40, D37075 Göttingen, Germany. rdiem@gwdg.de
Taheri
Naimeh
N
Dietz
Gunnar P H
GP
Kuhnert
Antje
A
Maier
Katharina
K
Sättler
Muriel B
MB
Gadjanski
Ivana
I
Merkler
Doron
D
Bähr
Mathias
M
D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005074:Evoked Potentials, Visual / Q000187:drug effects / Q000235:genetics; D005260:Female; D015696:Gene Products, tat / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use; D005822:Genetic Vectors / Q000235:genetics; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D009900:Optic Nerve / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009902:Optic Neuritis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D011914:Rats, Inbred BN; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D014161:Transduction, Genetic / Q000379:methods; D016896:Treatment Outcome; D051020:bcl-X Protein / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use
D015696:Gene Products, tat; D011993:Recombinant Fusion Proteins; D051020:bcl-X Protein