Atypical gliosis in Muller cells of the slowly degenerating rds mutant mouse retina

Retinal Muller glial cells are known to undergo reactive changes (gliosis) in various retinal diseases. In virtually all cases studied, an upregulation of glial fibrillary acidic protein (GFAP) and a hypertrophy can be observed. Physiological alterations, such as a strong downregulation of inwardly rectifying K+ (Kir) currents, were found after retinal detachment (man, rabbit) and after ischemia/reperfusion (rat) but not in more slowly progressing retinal degenerations (Borna Disease Virus-infected rats, RCS rats). This led us to hypothesize that Muller cells respond with 'typical' reactive gliosis only to rapid but not to slow retinal degeneration. To test this hypothesis, we studied Muller cells from rds mutant mice (Prph(Rd2)), Which show a retinal degeneration of early onset and slow progression, resulting in a complete loss of photoreceptors after 9-12 months. In Muller cells of rds mice, we found immunoreactivity for GFAP, a marker of gliosis in Muller cells, from postnatal day 21 on, accompanied by a moderately increased membrane capacitance (taken as an indicator of hypertrophy), whereas no change in the expression of the Kir4.1 protein occurred in adult rds mice. We failed to observe significant changes in the membrane resistance and the membrane potential of cells from rds mice from first week after birth until 1 year of age. Current densities were decreased in cells from 3- and 5-week old rds mice. Furthermore, as in control cells from wildtype animals, these cells displayed dominant Kir currents, voltage-dependent Na+ currents, and glutamate uptake currents. These data support the idea that in mice as well as previously shown in rats, slow retinal degeneration induces an atypical gliosis of Muller cells. (c) 2005 Elsevier Ltd. All rights reserved.