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Retinal gliopathy accompanying thioacetamide-induced liver insufficiency: light and electron microscopic observations
J Albrecht1, R Gadamski, H Kuhrt
1Medical Research Center, Polish Academy of Sciences, Warsaw.
Abstract:
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 Müller 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 Müller cells were examined in rats in which LI with accompanying HE was induced with a hepatotoxin, thioacetamide (TAA). Light microscopically, retinae of rats with LI were characterized by swelling of the Muller cell cytoplasm. Immunostaining for glia-specific marker proteins in Müller 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 Müller 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.
Insights
Liver insufficiency (LI) causes retinal Müller glia changes similar to hepatic encephalopathy (HE) in humans. A rat model with induced LI showed similar retinal Müller cell alterations, supporting its use for studying hepatic retinopathy (HR).
Area of Science:
- Ophthalmology
- Hepatology
- Neuroscience
Background:
- Liver insufficiency (LI) with hepatic encephalopathy (HE) is associated with astrocytic changes.
- Morphological alterations in retinal Müller glia were observed in patients with LI and HE, leading to the term "hepatic retinopathy" (HR).
Purpose of the Study:
- To investigate the immunomorphology and ultrastructure of Müller cells in a rat model of LI with HE.
- To establish a suitable animal model for studying the pathomechanisms of hepatic retinopathy.
Main Methods:
- Induction of LI and HE in rats using the hepatotoxin thioacetamide (TAA).
- Light microscopy and immunostaining for glial fibrillary acidic protein and glutamine synthetase in retinal Müller cells.
- Ultrastructural examination of Müller cells, including cell processes and endfeet.
Main Results:
- LI in rats induced swelling of Müller cell cytoplasm and enhanced expression of glial fibrillary acidic protein and glutamine synthetase.
- Ultrastructural analysis revealed swelling and vacuolization of Müller cell processes, with swollen mitochondria in endfeet.
- No significant morphological changes were observed in retinal neurons or photoreceptor cells.
Conclusions:
- The retinal Müller cell changes in the TAA-induced rat model closely resemble those observed in human hepatic retinopathy.
- This rat model is suitable for further research into the pathomechanisms of hepatic retinopathy.