Neuroprotective Effect of Rapamycin in Optic Nerve Transection Model

PURPOSE: The present study investigated whether rapamycin activated autophagy in retinal ganglion cells (RGC) and evaluated its effect on RGC survival following optic nerve transection (ONT). METHODS: The activation of autophagy in RGCs after intravitreal injection of rapamycin was evaluated with the immunohistochemical staining of phospho-S6 ribosomal protein. Rapamycin or 0.1% DMSO was injected intravitreally immediately after ONT. At 1 and 2 weeks after ONT, the RGCs were counted. Rapamycin and autophagy inhibitors, 3-methyladenine or Wortmannin were co-injected intravitreally after ONT and the RGCs were counted 1 week later. RESULTS: Expression of phospho-S6 ribosomal protein was decreased in RGCs after intravitreal injection of rapamycin. The RGC number was significantly higher in the rapamycin group than in the control group 1 week after ONT. However, the RGC number was not different between the 2 groups 2 weeks after ONT. Repeated intravitreal injection of rapamycin at 1-week intervals showed neuroprotection 2 weeks after ONT. The RGC number was not different between the control group and the co-injection group of rapamycin-autophagy inhibitor. CONCLUSIONS: Activated autophagy by rapamycin was neuroprotective in RGC after ONT.

Morphological Changes of the Dopaminergic Network in the Rat Retina after Axotomy / 대한해부학회지

In the retina, dopaminergic cells express the receptor for brain-derived neurotrophic factor (BDNF), which is known to be retrogradely transported from higher center to the retina. This study was conducted to identify the effect of optic nerve transaction on the dopaminergic cells in the rat retina by immunocytochemistry using antityrosine hydroxylase (TH) antiserum. In the control retina, we found two types of TH-immunoreactive amacrine cells, type I and type II, in the inner nuclear layer (INL) adjacent to the inner plexiform layer (IPL). The type I amacrine cell varicosities formed ring-like structures in contact with AII amacrine cell somata in stratum 1 of the IPL. In the axotomized retinas, TH-labeled processes formed loose networks of fibers, unlike the dense networks in the control retina, and the ring-like structures were disrupted. Our data suggest that retrogradely transported neurotrophic factor affects the expression of TH immunoreactivity in the axotomized rat retina and may therefore influence the retinal dopaminergic system.