Table 1.
Summary of LBP pre-treatment outcomes in experimental models of optic nerve insult
| Experimental model / species | LBP treatment (Duration) | Structural outcomes | Functional outcomes | Key findings and possible mechanisms of RGC neuroprotection | Reference |
|---|---|---|---|---|---|
| Chronic ocular hypertension (COH) | |||||
| Laser photocoagulation of episcleral and limbal veins in SD rat | Pre-treatment (–1 to 4 weeks) | LBP preserved RGC at both week 2 and 4 | Not assessed (n/a) | LBP treatment (0.01, 0.1, 1, 10, 100, and 1000 mg/kg) exhibited a U-shaped dose-response on RGC survival. Maximum RGC protection was achieved at 1 and 10 mg/kg LBP LBP did not alter the elevated IOP levels | Chan et al., 2007 |
| Laser photocoagulation of episcleral and limbal veins in SD rat | Pre-treatment (–1 to 4 weeks) | LBP preserved RGC at both week 2 and 4 | n/a | LBP modulated the microglial activation in the inner retinal layers in a dose-response manner. Moderately activated microglia observed at 1 and 10 mg/kg LBP offered maximum RGC protection than highly activated at 1000 mg/kg LBP | Chiu et al., 2009 |
| Laser photocoagulation of episcleral and limbal veins in SD rat | Pre-treatment (–1 to 2 weeks) | LBP preserved RGC | n/a | LBP modulated retinal crystalline proteins levels (mainly βB2), which was otherwise downregulated under IOP stress conditions | Chiu et al., 2010 |
| Laser photocoagulation of episcleral and limbal veins in SD rat | Pre-treatment (–1 to 2 weeks) | LBP preserved RGC | n/a | LBP modulated the expressions of ET-1 and its receptors in both RGCs and retinal vasculature, which improved RGC survival | Mi et al., 2012b |
| Acute ocular hypertension (AOH) | |||||
| AOH of 90 mmHg x 60 minutes in C57 mouse | Pre-treatment (–7 to 7 days) | LBP retained ~88% of IRL thickness and reduced RGC loss (LBP vs. PBS: ~15% vs. ~38%) | n/a | LBP protected blood retinal barrier by increasing the expression of occludin and preserving the tight junctions LBP maintained the blood vessel density by down-regulating the expressions of ET-1, receptors of advanced glycation end products (RAGE), advanced glycation end products, and amyloid beta protein | Mi et al., 2012a |
| AOH of 90 mmHg x 60 minutes in C57 mouse | Pre-treatment (–7 to 4 days) | n/a | n/a | LBP reduced AOH-induced retinal gliosis by decreasing the expressions of glial fibrillary acidic protein (GFAP), glutamine synthetase, aquaporin-4 (AQP-4), S-100 proteins, iba-1, RAGE and amyloid precursor protein | Mi et al., 2020 |
| AOH of 130 mmHg x 60 minutes in SD rat | Pre-treatment (–7 to 7 days) | LBP reduced RGC loss (LBP vs PBS: ~40% vs. ~70%) | n/a | LBP enhanced the adaptive Nrf2/HO-1 anti-oxidant pathway which reduced the rate of ROS generation and improved RGC survival | He et al., 2014 |
| Ischemic-reperfusion retinal injury | |||||
| Surgically occlusion of right internal carotid artery for 2 hours in C57 mouse | Pre-treatment (–7 to 1 days) | LBP prevented retinal swelling, reduced RGC apoptosis, and retained 97% of the GCL cell density | n/a | LBP reduced the level of oxidative stress, the expressions of GFAP and AQP4, and the blood vessel leakages | Li et al., 2011a |
| Partial or complete optic nerve transaction (PONT/CONT) | |||||
| CONT/PONT in SD rat | Pre-treatment (–1 to 2/4 weeks) | LBP did not prevent primary/secondary degeneration of RGC in CONT model, but improved the RGC survival at the site of secondary degeneration in PONT model | n/a | LBP upregulated the expressions of oxidative enzyme and insulin growth factor-1, and downregulated the pro-apoptotic JNK signalling pathway | Li et al., 2013 |
| PONT in SD rat | Pre-treatment (–1 to 4 weeks) | LBP reduced the axonal loss at the site of secondary degeneration | n/a | LBP reduced the activation of microglial/ macrophages in the optic nerve | Li et al., 2015 |
| Temporal ONT in SD rat | Pre-treatment (–1 to 4 weeks) | LBP delayed the secondary degeneration of RGC | n/a | LBP increased the expression of M2 types of microglia/ macrophages, which promoted the levels of anti-inflammatory cytokines and reduced autophagy levels | Li et al., 2019 |
| PONT in SD rat | Pre-treatment (–1 to 4 weeks) | n/a | LBP treatment resulted in the showed a recovery of inner retinal functions by mfERG (P1, PhNR) at both sites of primary and secondary degeneration | Chu et al., 2013 |
AOH: Acute ocular hypertension; AQP: aquaporin; ET: Endothelin; ERG: electroretinogram; GCL: ganglion cell layer; IOP: intraocular pressure; LBP: Lycium barbarum polysaccharides; PBS: phosphate-buffered solution; PhNR: photopic negative response; RGC: retinal ganglion cells; SD: Sprague-Dawley.