The effects of FK506 on retinal ganglion cells after optic nerve crush.
OBJECTIVE
The purpose of this study was twofold: to determine whether immunophilins were present in the rat retina and to determine the physiologic consequence of their presence.


METHODS
Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis were performed on rat retinal tissue, and the immunophilin FKBP12 was found to be present in retina. Immunohistochemical studies showed the presence of FKBP12 in retinal ganglion cells (RGCs). In rats, optic nerve crush was performed on one side and a sham operation on the other side. By gavage, animals were given 5 mg/kg per day of the FKBP12 ligand FK506 in sterile phosphate-buffered saline (PBS) or in PBS alone. Eight days after nerve crush, the total number of back-labeled RGCs was estimated from retinal wholemounts.


RESULTS
In control eyes, the number of labeled ganglion cells was 74,104 +/- 4,166 (mean +/- SEM) in rats receiving vehicle and 74,993 +/- 3,098 in animals receiving FK506 daily. Eight days after optic nerve crush, 27,775 +/- 3,332 labeled ganglion cells were counted in retinas of animals receiving vehicle (n = 11), whereas 33% more ganglion cells (37,118 +/- 2,475) were counted in animals receiving FK506 daily (n = 11). This difference was statistically significant (P < 0.05).


CONCLUSIONS
The data presented demonstrate that the immunophilin FKBP12 is present in retina and specifically in RGCs. In addition, the FKBP12 ligand FK506 confers neuroprotection on RGCs after optic nerve crush. This neuroprotection may occur as a result of FK506's ability to interfere with apoptotic mechanisms after optic nerve crush.
Freeman
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EE
Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston 02114, USA.
Grosskreutz
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CL
D000818:Animals; D015153:Blotting, Western; D002452:Cell Count; D017931:DNA Primers / Q000737:chemistry; D019084:Fluorescent Antibody Technique, Indirect; D020104:Immunophilins / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D009409:Nerve Crush; D009900:Optic Nerve / Q000502:physiology* / Q000601:surgery; D051381:Rats; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016559:Tacrolimus / Q000494:pharmacology*; D022021:Tacrolimus Binding Proteins
D017931:DNA Primers; D007166:Immunosuppressive Agents; D022021:Tacrolimus Binding Proteins; D020104:Immunophilins; D016559:Tacrolimus