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Time course degeneration and expression of glial fibrillary acidic protein in mer-knockout mice
Xiao-Ying Liang1, Huai-Zhou Wang, Ning-Li Wang
1Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing 100730, China.
Background:
Müller cells in the mammalian retina normally express low levels of glial fibrillary acidic protein (GFAP); however, its expression is upregulated in response to the loss of retinal neurons. The change in expression of GFAP is one of the earliest indicators of retinal damage and is correlated with the time course of disease. The aim of this study was to investigate the time course of degeneration and the expression of GFAP in the retina of mer knockout mice.
Methods:
A total of 30 mer knockout mice, aged from 15 - 20 days to 1 year and 32 age-matched wild type mice as controls were tested. Immunohistochemistry was used to show the expression of GFAP in the central and peripheral retina of mer knockout and control mice at postnatal age of 15 days (P15d), 20 days (P20d), 4 weeks (P4w), 6 weeks (P6w), 8 weeks (P8w), 3 months (P3m), 6 months (P6m) and 1 years (P1y).
Results:
The expression of GFAP in the central and peripheral retina of wild type mice was limited to the retinal ganglion cell and nerve fiber layers. In the central retina of mer knockout mice, GFAP expression was upregulated at P4w and GFAP immunolabelling penetrates across the entire thickness of the retina at P8w; whereas in the peripheral retina, the GFAP expression was upregulated at P20d and GFAP immunolabelling penetrates the entire retina after P4w.
Conclusions:
Increased expression of GFAP in Müller cells of mer knockout mice occur at P20d in the peripheral retina and P4w in the central retina. GFAP expression in Müller cells appears to be a secondary response to the loss of retinal neurons. Increased expression of GFAP may occur prior to any detectable morphological changes in the retina. This study suggests that the loss of retinal neurons may begin in the early stages of retinitis pigmentosa, prior to the discovery of any morphological changes in the retina.
Insights
Glial fibrillary acidic protein (GFAP) in Müller cells increases early in mer knockout mice, indicating potential neuron loss before visible retinal changes. This suggests GFAP upregulation is a key indicator of early-stage retinal degeneration.
Area of Science:
- Neuroscience
- Ophthalmology
- Cell Biology
Background:
- Müller cells in the mammalian retina normally express low levels of glial fibrillary acidic protein (GFAP).
- GFAP expression is upregulated in response to retinal neuron loss and serves as an early indicator of retinal damage.
- The study investigates the time course of GFAP expression changes in mer knockout mice, a model for retinal degeneration.
Purpose of the Study:
- To investigate the time course of retinal degeneration in mer knockout mice.
- To analyze the expression patterns of GFAP in the retina of mer knockout mice.
- To correlate GFAP upregulation with early signs of retinal damage.
Main Methods:
- Utilized immunohistochemistry to detect GFAP expression.
- Examined both central and peripheral retina in mer knockout and wild-type mice.
- Assessed GFAP expression at multiple time points from postnatal day 15 to 1 year.
Main Results:
- In wild-type mice, GFAP expression was confined to the retinal ganglion cell and nerve fiber layers.
- In mer knockout mice, GFAP expression upregulated at postnatal day 20 (P20d) in the peripheral retina and at 4 weeks (P4w) in the central retina.
- GFAP immunolabelling penetrated the entire retinal thickness by P8w in the central retina and after P4w in the peripheral retina.
Conclusions:
- Increased GFAP expression in Müller cells of mer knockout mice occurs early (P20d peripheral, P4w central).
- GFAP upregulation is a secondary response to retinal neuron loss.
- Elevated GFAP may precede detectable morphological changes, suggesting early neuronal loss in retinitis pigmentosa.
