Retinal and optic nerve degeneration in liver X receptor β knockout mice.
Xiao-Yu SongWan-Fu WuChiara GabbiYu-Bing DaiMark SoSurendra P ChaurasiyaLi WangMargaret WarnerJan-Åke GustafssonPublished in: Proceedings of the National Academy of Sciences of the United States of America (2019)
The retina is an extension of the brain. Like the brain, neurodegeneration of the retina occurs with age and is the cause of several retinal diseases including optic neuritis, macular degeneration, and glaucoma. Liver X receptors (LXRs) are expressed in the brain where they play a key role in maintenance of cerebrospinal fluid and the health of dopaminergic neurons. Herein, we report that LXRs are expressed in the retina and optic nerve and that loss of LXRβ, but not LXRα, leads to loss of ganglion cells in the retina. In the retina of LXRβ-/- mice, there is an increase in amyloid A4 and deposition of beta-amyloid (Aβ) aggregates but no change in the level of apoptosis or autophagy in the ganglion cells and no activation of microglia or astrocytes. However, in the optic nerve there is a loss of aquaporin 4 (AQP4) in astrocytes and an increase in activation of microglia. Since loss of AQP4 and microglial activation in the optic nerve precedes the loss of ganglion cells, and accumulation of Aβ in the retina, the cause of the neuronal loss appears to be optic nerve degeneration. In patients with optic neuritis there are frequently AQP4 autoantibodies which block the function of AQP4. LXRβ-/- mouse is another model of optic neuritis in which AQP4 antibodies are not detectable, but AQP4 function is lost because of reduction in its expression.
Keyphrases
- optic nerve
- optical coherence tomography
- cell cycle arrest
- induced apoptosis
- cell death
- endoplasmic reticulum stress
- oxidative stress
- resting state
- diabetic retinopathy
- white matter
- inflammatory response
- cerebrospinal fluid
- neuropathic pain
- signaling pathway
- functional connectivity
- systemic lupus erythematosus
- multiple sclerosis
- mental health
- poor prognosis
- spinal cord injury
- climate change
- lps induced
- long non coding rna
- human health
- binding protein
- age related macular degeneration