Retinal gliopathy accompanying thioacetamide-induced liver insufficiency: light and electron microscopic observations

A recent examination of retinae of patients who had died with symptoms of liver insufficiency (LI) including hepatic encephalopathy (HE) revealed morphological changes in retinal Muller glia similar to the astrocytic changes normally accompanying HE, and the term "hepatic retinopathy" (HR) was coined to define these changes. In the present study, the immunomorphology and ultrastructure of Muller cells were examined in rats in which LI with accompanying HE was induced with a hepatotoxin, thioacetamide (TAA). Light microscopically, retinae of rats with LT were characterized by swelling of the Muller cell cytoplasm. Immunostaining for glia-specific marker proteins in Muller cells from LI rats revealed a strongly enhanced expression of glial fibrillary acidic protein, and a considerable increase in glutamine synthetase immunoreactivity, as compared to control animals. Ultrastructurally, the Muller cells of LI rats showed swelling and vacuolization of cell processes. In particular, the endfeet contained many swollen mitochondria. By contrast, LI produced no morphologically demonstrable changes in retinal neurons and photoreceptor cells. Thus, the retinal changes induced by TAA in the rats strongly resembled those described in human HR, rendering the present rat model suitable for more detailed investigations of the pathomechanism(s) of HR.