Complete or partial optic nerve transaction
The partial optic nerve transection (PONT) model allows good separation of secondary degeneration from the directly injured RGCs. Li et al80 investigated the protective effects of LBPs on RGCs in Sprague–Dawley rats subject to complete or partial optic nerve transection (CONT or PONT). Rats were administered with 1 mg/kg/day LBPs for 7 days before surgery until sacrificed at different time points. The expression levels of several proteins related to inflammation, oxidative stress, and Jun N-terminal kinases (JNK)/c-Jun pathway were determined using Western blotting assay. LBPs did not delay primary degeneration of RGCs after either CONT or PONT, but delayed secondary degeneration of RGCs after PONT.80 These results demonstrate that LBPs decrease secondary degeneration of RGCs by inhibiting oxidative stress and the JNK/c-Jun pathway and by transiently increasing the expression of insulin-like growth factor-1 (IGF-1).
Chu et al also investigated the retinal protective effects of LBPs in rat PONT model when the multifocal electroretinograms (mfERGs) were recorded in Sprague–Dawley rats.81 The mfERG allows for recording multiple local retinal responses within a short time period, and it is widely used in glaucoma investigation in animal and human studies. The rats were administered 1 mg/kg LBP via a nasogastric tube every day until euthanization. The PONT surgery was performed at day 7 after start of LBP dosing. As with the primate mfERG response, the waveform in rats contains a trough (N1) at around 25 milliseconds, followed by a major positive component (P1) at around 55 milliseconds, and a photopic negative response (PhNR) that can be observed at around 75 milliseconds.81 The topographical mfERG response demonstrated a stronger retinal function along the visual streak with a peak in the nasal field in both conditions with and without PONT. After administering 1 mg/kg LBP a week prior to PONT surgery, the rats showed increased N1 responses, P1 responses, and PhNRs, especially in the inferior retina when compared with the control group. The N1 amplitudes were significantly increased at week 4 after PONT except in the superior regions.81 The P1 amplitude in the far superior region showed a significant reduction 1 week after PONT, but then returned to the normal range. P1 amplitudes remained normal in other regions after PONT but were significantly increased in the inferior retina 4 weeks after PONT. The PhNR amplitude reduced significantly in the superior retina 1 week after PONT and then gradually returned to the normal range. The PhNR amplitude in the inferior retina appeared to be increased after PONT with prolonged feeding with LBPs, but this effect was not statistically significant. These results show that LBPs reduce the deterioration of retinal function after PONT through unknown mechanisms.