Hepatic retinopathy: morphological features of retinal glial (M�ller) cells accompanying hepatic failure

Abstract

More than 80 years ago, Alzheimer described changes in the brains of patients who had suffered hepatic failure. Astrocytes are primarily affected; their nuclei become swollen, their intermediate filament protein composition is altered and their cytoplasm becomes vacuolated. Cells with these features are called Alzheimer type II astrocytes and these changes have been attributed to the toxic effects of elevated ammonia levels. The present study investigates whether the dominant glia of another part of the central nervous system, the Müller cells of the retina, undergo similar changes. Retinae of patients who had died with symptoms of hepatic failure were processed for histology, histochemistry, and immunocytochemistry. Cell nuclei were measured from brain astrocytes (insula cortex), Müller cells, and retinal bipolar neurons. Hepatic failure resulted in the enlargement of nuclei in astrocytes and Müller cells, and the enhanced expression in Müller cells of glial fibrillary acidic protein, cathepsin D, and the beta-subunit of prolyl 4-hydroxylase (glial-p55). In some retinae, signs of gliosis were also observed. We conclude that increased levels of serum ammonia resulting from hepatic insufficiency cause changes in Müller cells that are similar to those seen in brain astrocytes. We term this condition hepatic retinopathy.

High prevalence of sleep disturbance in cirrhosis

“…7 The inversion of sleep pattern described in patients with overt encephalopathy 1 could be an extreme of this displacement. Several mechanisms may be involved in the development of circadian abnormalities in cirrhosis, including the effect of gut-derived toxins on the brain 36 and decreased sensorial inputs that entrain the circadian clock 37 such as insufficient light exposure, social isolation, or low levels of activity and retinohypothalamic 38 and endocrine (e.g., melatonin) abnormalities.…”

Critical flicker frequency for quantification of low-grade hepatic encephalopathy

“…25 Such events may also take place in the retina and may underlie so-called hepatic retinopathy, 26,27 in which retinal glial (Müller) cells may exhibit morphologic changes similar to Alzheimer type II astrocytes. 26 Based on the hypothesis that retinal gliopathy could serve as a marker of cerebral gliopathy in HE, we investigated whether assessment of visual function by determining the critical flicker-fusion frequencies is suitable for diagnosis and quantification of low-grade HE.…”

“…25 Such events may also take place in the retina and may underlie so-called hepatic retinopathy, 26,27 in which retinal glial (Müller) cells may exhibit morphologic changes similar to Alzheimer type II astrocytes. 26 Based on the hypothesis that retinal gliopathy could serve as a marker of cerebral gliopathy in HE, we investigated whether assessment of visual function by determining the critical flicker-fusion frequencies is suitable for diagnosis and quantification of low-grade HE. Such tests have not yet been applied to HE patients, but there is a long-standing experience with the flicker-fusion frequency analysis in cerebro-organic syndromes, 28 multiple sclerosis, 29 Alzheimer's disease, 30 and the testing of psychoactive drugs.…”

Validity of Inhibitory Control Test and Critical Flicker Frequency to Diagnose Minimal Hepatic Encephalopathy

“…The ROC curve had an area under the curve of 0.87 (95% CI 0.83-0.92) for MHE diagnosis. [12][13][14] . The underlying thought is that retinal gliopathy could serve as a marker of cerebral gliopathy occurring in HE, and has been investigated in patients with low-grade HE.…”