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Abstract #5831 Published in IGR 2-1
The effects of FK506 on retinal ganglion cells after optic nerve crush
Freeman EE; Grosskreutz CLInvestigative Ophthalmology and Visual Science 2000; 41: 1111-1115
PURPOSE: The purpose of this study was twofold: to determine whether immunophilins were present in the rat retina, and to determine the physiological 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 present of FKBP12 in retinal ganglion cells (RGCs). In rats, optic nerve crush was performed on one side and a sham operation on the other. 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-labelled RGCs was estimated from retinal wholemounts. RESULTS: In control eyes, the number of labelled 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 labelled ganglion cells were counted in retinas of animals receiving vehicle (n=110, whereas 33% more ganglion cells (37,118±2,745) 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.
Dr. C.L. Grosskreutz, Glaucoma Consultation Service, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114, USA. cynthia_grosskreutz@meei.harvard.edu
Classification:
11.8 Neuroprotection (Part of: 11 Medical treatment)
