Protection of retinal ganglion cells and retinal vasculature by Lycium barbarum polysaccharides in a mouse model of acute ocular hypertension

PLoS One. 2012;7(10):e45469. doi: 10.1371/journal.pone.0045469. Epub 2012 Oct 19.

Abstract

Acute ocular hypertension (AOH) is a condition found in acute glaucoma. The purpose of this study is to investigate the protective effect of Lycium barbarum polysaccharides (LBP) and its protective mechanisms in the AOH insult. LBP has been shown to exhibit neuroprotective effect in the chronic ocular hypertension (COH) experiments. AOH mouse model was induced in unilateral eye for one hour by introducing 90 mmHg ocular pressure. The animal was fed with LBP solution (1 mg/kg) or vehicle daily from 7 days before the AOH insult till sacrifice at either day 4 or day 7 post insult. The neuroprotective effects of LBP on retinal ganglion cells (RGCs) and blood-retinal-barrier (BRB) were evaluated. In control AOH retina, loss of RGCs, thinning of IRL thickness, increased IgG leakage, broken tight junctions, and decreased density of retinal blood vessels were observed. However, in LBP-treated AOH retina, there was less loss of RGCs with thinning of IRL thickness, IgG leakage, more continued structure of tight junctions associated with higher level of occludin protein and the recovery of the blood vessel density when compared with vehicle-treated AOH retina. Moreover, we found that LBP provides neuroprotection by down-regulating RAGE, ET-1, Aβ and AGE in the retina, as well as their related signaling pathways, which was related to inhibiting vascular damages and the neuronal degeneration in AOH insults. The present study suggests that LBP could prevent damage to RGCs from AOH-induced ischemic injury; furthermore, through its effects on blood vessel protection, LBP would also be a potential treatment for vascular-related retinopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Blood-Retinal Barrier / drug effects
  • Blood-Retinal Barrier / metabolism
  • Blood-Retinal Barrier / pathology
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Drugs, Chinese Herbal / pharmacology*
  • Drugs, Chinese Herbal / therapeutic use
  • Endothelin-1 / genetics
  • Endothelin-1 / metabolism
  • Gene Expression / drug effects
  • Immunoglobulin G / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Degeneration / genetics
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / pathology
  • Nerve Degeneration / prevention & control*
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Ocular Hypertension / genetics
  • Ocular Hypertension / metabolism
  • Ocular Hypertension / pathology
  • Ocular Hypertension / prevention & control*
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism
  • Retinal Ganglion Cells / drug effects*
  • Retinal Ganglion Cells / metabolism
  • Retinal Ganglion Cells / pathology
  • Retinal Vessels / drug effects*
  • Retinal Vessels / metabolism
  • Retinal Vessels / pathology
  • Signal Transduction / drug effects
  • Tight Junctions / drug effects
  • Tight Junctions / metabolism
  • Tight Junctions / pathology

Substances

  • Amyloid beta-Peptides
  • Drugs, Chinese Herbal
  • Endothelin-1
  • Immunoglobulin G
  • Neuroprotective Agents
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic
  • lycium barbarum polysaccharide

Grants and funding

This study was supported by a GRF (General Research Fund) grant from Hong Kong Research Grant Council (National Basic Research Program of China (2011CB707501)), the fundamental Research Funds for The Central Universities (21609101), and Azalea (1972) Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.