Ciliary neurotrophic factor prevents the death of retinal ganglion cells in a rat glaucoma model

Abstract

The protective effect of ciliary neurotrophic factor (CNTF) on retinal ganglion cells (RGCs) in a rat glaucoma model with increased intraocular pressure (IOP) was investigated. Elevated IOP (about 1.5 times above normal) of the right eye in 36 SD rats was induced by laser photocoagulation of the episcleral and limbal veins. The laser treatments were done twice with 7 days separation. On the next day after the second laser treatment, the animals were divided into two groups. 2 µg CNTF (experimental) or 2 µl of PBS (control) was injected into the right eye. IOP of both eyes of each animal was measured once a week. One week before killing the animals, 6% Fluoro-Gold was applied to both superior colliculi. After a survival of 2, 4 or 8 weeks following the first laser treatment, both eyes were enulceated and the number of labelled RGCs was systematically counted in 4 quadrants of the retinas. In all groups, the changes in the densities of RGCs were expressed as % loss of RGCs comparing the laser treated and contralateral, control eyes from the same animal. There was a significant difference in the %RGC loss in the two weeks or 4 weeks groups between the CNTF and PBS animals. (2 weeks- CNTF: -7.4% and PBS: 12.6% (p<0.01); 4 weeks- CNTF: 4.6% and PBS:21.2%(p<0.01)). However, there was no significant difference in the RGC loss in the 8 weeks CNTF and PBS groups (CNTF:19.6% and PBS:25.8%, p>0.05). The IOP in the CNTF or PBS animals was maintained at an elevated level until 8 weeks. We concluded that CNTF injected intravitreally may provide protection against glaucoma–induced RGC death in rats up to 4 weeks. This effect was not due to a decrease in IOP.