Epigallocatechin Gallate Slows Retinal Degeneration, Reduces Oxidative Damage, and Modifies Circadian Rhythms in P23H Rats.

Lorena Perdices,Nicolás Cuenca,Isabel Pinilla,Elvira Orduna-Hospital,Lorena Fuentes-Broto,Francisco Segura

doi:10.3390/antiox9080718

Abstract

Retinitis pigmentosa (RP) includes a group of genetic disorders that involve the loss of visual function due to mutations mainly in photoreceptors but also in other retinal cells. Apoptosis, retinal disorganization, and inflammation are common in the progression of the disease. Epigallocatechin gallate (EGCG) has been proved as beneficial in different eye diseases. Pigmented heterozygous P23H rat was used as an animal model of RP. Visual function was assessed by optomotor and electroretinogram (ERG) and circadian rhythms were evaluated by telemetry. Hepatic oxidative damage and antioxidant defenses were assessed using biochemical tests. The visual function of the EGCG P23H group was preserved, with a deterioration in the activity period and lower values in the interdaily stability parameter. Control rats treated with EGCG were less active than the sham group. EGCG increased antioxidant levels in P23H rats but reduced total hepatic antioxidant capacity by almost 42% in control rats compared to the sham group. We conclude that treatment with EGCG improves visual function and antioxidant status in P23H rats but diminishes antioxidant defenses in wild-type control animals, and slightly worsens activity circadian rhythms. Further studies are necessary to clarify the beneficial effects in disease conditions and in healthy organisms.

Highlights

The human retina is a complex structure composed of different types of cells; perfect sight requires numerous connections between neurons and glial cells
Results are expressed in mM Trolox equivalents per mg of protein, with Trolox (238813, Sigma-Aldrich, Madrid, Spain) being a water-soluble tocopherol analogue used to standardize antioxidants
Data are presented as U/mg of protein, with one unit of superoxide dismutase (SOD) being the amount of enzyme that inhibits the rate of cytochrome c reduction by 50%

Summary

Introduction

The human retina is a complex structure composed of different types of cells; perfect sight requires numerous connections between neurons and glial cells. As a result of inherited diseases, physical damage, or other pathologies, produces changes in retinal circuitry and remodeling with the loss of visual function. Inherited retinal degenerative diseases, such as retinitis pigmentosa (RP), are caused by mutations in genes involved in visual function, generating a progressive loss of photoreceptors. Despite the genotypic heterogeneity in this disease, most patients are characterized by nyctalopia, a progressive loss of peripheral visual field, and bone spicules in the fundus. Antioxidants 2020, 9, 718 progression of RP, changes in color vision, visual field, visual acuity (VA), and electroretinogram (ERG). More than 60 genes can be affected by mutations, resulting in RP; one of the most studied genes is RHO, which encodes the rhodopsin protein, with more than 150 associated mutations currently identified [2]. P23H mutation is an autosomal-dominant RP commonly found in the USA [3]

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