Skip to main content
ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Virus and Prion Research » Research » Publications at this Location » Publication #129421
Title: ELECTROPHYSIOLOGICAL ALTERATIONS AND UPREGULATION OF ATP RECEPTORS IN RETINAL GLIAL MULLER CELLS FROM RATS INFECTED WITH THE BORNA DISEASE VIRUS

Author
item PANNICKE, T - UNIV LEIPZIG, GERMANY
item WEICK, M - UNIV LEIPZIG, GERMANY
item UCKERMANN, O - UNIV LEIPZIG, GERMANY
item WHEELER-SCHILLING, T - UNIV LEIPZIG, GERMANY
item FRIES, J - UNIV LEIPZIG, GERMANY
item REICHEL, M - UNIV LEIPZIG, GERMANY
item MOHR, C - UNIV LEIPZIG, GERMANY
item STAHL, T - UNIV LEIPZIG, GERMANY
item FLUESS, SEEGER,, REICHENBACH - UNIV LEIPZIG, GERMANY
item Richt, Juergen

Submitted to: Glia
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/1/2001
Publication Date: N/A
Citation: N/A

Interpretive Summary: Borna disease (BD) is a sporadically occurring, usually fatal polioencephalomyelitis that primarily affects horses and sheep. More rarely, a range of other domestic and zoo species and possibly humans are affected. The etiological agent of BD, the Borna Disease Virus (BDV), is an enveloped virus characterized by a non-segmented negative strand RNA genome ethat belongs to the new family Bornaviridae within the order Mononegavirales. As part of our ongoing studies on the retinal changes observed regularly after BDV-infection we found that despite the loss of most retinal neurons the dominating retinal macroglia, the Muller cells, do not degenerate. Electrophysiological analyses revealed that in BDV-induced retinopathy, reactive rat Muller cells change their physiological parameters but these changes are different from those in Muller cells during proliferative vitreoretinopathy in man and rabbit. This work on the electrophysiological properties of retinal cells after BDV-infection will lead to a better understanding how neurotropic viruses interact with host cells and will therefore help us to define areas for prophylactic intervention and treatment.

Technical Abstract: Infection with the neurotropic Borna disease virus (BDV) causes an immune-mediated neurological disease in a broad range of species. In addition to encephalitis, BDV-infected Lewis rats develop a retinitis histologically characterized by the loss of most retinal neurons. By contrast, the dominating retinal macroglia, the Muller cells, do not degenerate. It is known from several models of neurodegeneration that glia cells may survive but undergo significant alterations of their physiological parameters. This prompted us to study the electrophysiology and ATP-induced changes of intracellular Ca(2+)-concentration ([Ca(2+)](i)) in Muller cells from BDV-infected rat retinae. Freshly isolated cells were used for whole-cell patch-clamp recordings. Whereas neither zero current potentials nor membrane resistances showed significant alterations, the membrane capacitance increased in cells from BDV-infected rats during survival times of up to 8 months. This process was accompanied by a decrease in K(+) current densities. Muller cells from BDV-infected rats were characterized by expression of a prominent fast-inactivating A-type K(+) current which was rarely found in control cells. Moreover, the number of cells displaying Na(+) currents was slightly increased after BDV-infection. ATP evoked increases in [Ca(2+)](i) in Muller cells within retinal wholemounts of both control and BDV-infected animals. However, the number of ATP-responding isolated cells increased from 24% (age-matched controls) to 78% (cells from animals > or =18 weeks after infection). We conclude that in BDV-induced retinopathy, reactive rat Muller cells change their physiological parameters but these changes are different from those in Muller cells during proliferative vitreoretinopathy in man and rabbit.