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Ellen E. Freeman, Cynthia L. Grosskreutz; The Effects of FK506 on Retinal Ganglion Cells after Optic Nerve Crush. Invest. Ophthalmol. Vis. Sci. 2000;41(5):1111-1115.
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purpose. 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
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
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