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Age- and disease-related changes of calcium channel-mediated currents in human Müller glial cells
A Bringmann1, B Biedermann, U Schnurbusch
1Department of Neurophysiology, Paul Flechsig Institute of Brain Research, University of Leipzig, Germany. bria@server3.medizin.uni-leipzig.de
Purpose:
To determine whether the expression of voltage-gated Ca2+ channels in human Müller glial cells changes during normal aging and in cells from patients with proliferative vitreoretinopathy (PVR).
Methods:
Müller cells were enzymatically isolated from retinas of healthy donors and from excised retinal pieces of patients with PVR, and the whole-cell, voltage-clamp technique was used to characterize the current densities of transient, low-voltage-activated calcium channels and of sustained. high-voltage-activated calcium channels, respectively. To obtain maximal currents through both channel types, Na+ ions were used as the charge carrier.
Results:
During normal aging, Müller cells developed a hypertrophy, as indicated by an increase of the cell membrane capacitance. The mean membrane capacitance of cells from aged donors (> or = 60 years old) was elevated by 25% compared with cells from younger donors. The hypertrophy was not accompanied by a changed density of low-voltage-activated currents, whereas the density of the high-voltage-activated currents was enhanced by 76%. The density of the high-voltage-activated currents increased in correlation with the increase of the cell membrane capacitance and with the age of the donors. In the case of PVR, Müller cells displayed a strong hypertrophy accompanied by a downregulation of both current types by approximately 65%.
Conclusions:
Both normal aging and PVR cause a gliotic reactivity of human Müller cells, as indicated by their hypertrophy. The type of reactivity, however, differs between the two conditions. Normal aging is accompanied by an increased expression of voltage-gated Ca2+ channels, whereas in PVR Ca2+ channel expression is decreased.
Insights
Normal aging increases voltage-gated calcium channel expression in human Müller glial cells, while proliferative vitreoretinopathy (PVR) decreases it. Both conditions induce cell hypertrophy, indicating gliotic reactivity.
Area of Science:
- Ophthalmology
- Neuroscience
- Cell Biology
Background:
- Müller glial cells are crucial for retinal function and homeostasis.
- Changes in Müller cell properties are implicated in retinal aging and disease.
- Voltage-gated calcium channels play a role in cellular excitability and signaling.
Purpose of the Study:
- To investigate alterations in voltage-gated calcium channel expression in human Müller glial cells.
- To compare these changes in normal aging versus proliferative vitreoretinopathy (PVR).
Main Methods:
- Human Müller cells were isolated from healthy donors and PVR patients.
- Whole-cell, voltage-clamp technique was employed to measure calcium channel current densities.
- Sodium ions were used as charge carriers to maximize currents.
Main Results:
- Normal aging correlated with Müller cell hypertrophy and a 76% increase in high-voltage-activated calcium currents.
- Proliferative vitreoretinopathy (PVR) induced significant hypertrophy and a ~65% downregulation of both low- and high-voltage-activated calcium currents.
- Cell membrane capacitance increased with age, correlating with enhanced high-voltage-activated currents.
Conclusions:
- Both normal aging and PVR induce gliotic reactivity in human Müller cells, characterized by hypertrophy.
- Normal aging leads to increased expression of voltage-gated calcium channels.
- PVR is associated with decreased expression of voltage-gated calcium channels.