Abstract

Swelling of retinal Müller cells is implicated in retinal edema and neuronal degeneration. Müller cell swelling is observed in patients with liver failure and is referred to as hepatic retinopathy. In the present study, we evaluated the effects of aloin, an anthraquinone-C-glycoside present in various Aloe species, on Müller cell dysfunction in a rat model of thioacetamide (TAA)-induced hepatic retinopathy. Experimental hepatic retinopathy was induced by three injections of TAA (200 mg/kg/day, intraperitoneal injection) for 3 days in rats. After the last injection of TAA, aloin (50 and 100 mg/kg) was orally gavaged for 5 days. The effects of aloin on the liver injury, serum ammonia levels, Müller cell swelling, glial fibrillary acidic protein (GFAP) expression, and gene expression of Kir4.1 and aquaporin-4 were examined. TAA-injected rats exhibited liver failure and hyperammonemia. In the TAA-injected rats, Müller cell bodies were highly enlarged, and GFAP, an indicator of retinal stress, was highly expressed in the retinas, indicating a predominant Müller cell gliosis. However, administration of aloin suppressed liver injury as well as Müller cell swelling through the normalization of Kir4.1 and aquaporin-4 channels, which play a key role in potassium and water transport in Müller cells. These results indicate that aloin may be helpful to protect retinal injury associated with liver failure.

Highlights

  • The liver is an important vital organ and has the greatest capacity to eliminate harmful toxins and produce useful substances essential to the human body [1]

  • Müller cells control ion balance [7] and maintain homeostasis of water content in the retinal tissues [8]. When this supportive activity of Müller cells is altered under disease conditions, such as hepatic retinopathy, diabetes-induced retinal dysfunction, and age-related macular degeneration, Müller cells contribute to a dysregulation of metabolism and water homeostasis, resulting in the development of retinal edema and neuronal cell injury [9]

  • We showed that aloin, a bioactive compound present in various Aloe species, prevented Müller cell swelling induced by liver cirrhosis in a rat model with TAA-induced hepatic retinopathy

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Summary

Introduction

The liver is an important vital organ and has the greatest capacity to eliminate harmful toxins and produce useful substances essential to the human body [1]. Hyperammonemia resulting from liver failure cause morphological alterations in Müller cells in the retina This is called hepatic retinopathy [4,5]. Müller cells control ion balance [7] and maintain homeostasis of water content in the retinal tissues [8] When this supportive activity of Müller cells is altered under disease conditions, such as hepatic retinopathy, diabetes-induced retinal dysfunction, and age-related macular degeneration, Müller cells contribute to a dysregulation of metabolism and water homeostasis, resulting in the development of retinal edema and neuronal cell injury [9]. According to these previous reports, it is hypothesized neuronal cell death after cerebral ischemia [22] According to these previous reports, it is that aloin may have a potent inhibitory effect on hepatic retinopathy.

Histopathological Changes in Liver
Serum Ammonia Levels
Müller Cell Activation
Retinal
Discussion
Animals and Experimental Design
Evaluation of Liver Injury
Isolation of Rat Retinal Müller Cells
Immunohistochemical Staining
Real-Time PCR
Statistical Analysis

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