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

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.

Keywords: P23H rat; antioxidant therapy; circadian rhythm; epigallocatechin gallate; green tea; neurodegenerative model; oxidative damage; retinal degeneration; retinitis pigmentosa; visual function.

Figure 1

Values of (a) visual acuity (VA) and (b) contrast sensitivity (CS) at 30, 60, 90 and 180 postnatal days in P23H and Sprague–Dawley (SD) × Long Evans (LE) treatment groups, obtained by the optomotor system on average between the clockwise and anti-clockwise directions. Data represent the mean ± standard error (n = 5 per group). Mann–Whitney U test, * p < 0.05 versus P23H-vehicle animals, # p < 0.05 versus SD × LE animals.

Figure 2

Scotopic (a) a- and (b) b-wave responses for flash intensities of 0.0002, 0.0015, 0.0092, 0.06, 0.38, 2.38, 23.19, 78, and 722 cd.s/m² and electroretinogram double flash protocol (at 1.4 log cd.s/m²) (c) recorded at P180 in P23H and SD × LE treatment groups. Data are presented as mean ± standard error (n = 5 per group). Mann–Whitney U test, * p < 0.05 versus P23H-vehicle animals, # p < 0.05 versus SD × LE animals.

Figure 3

Representative actograms (left), periodograms (middle), and mean waveforms (right) obtained analyzing core-body temperature rhythms at P180 in P23H and SD × LE rats without treatment. The light/dark cycle is represented by white and dark horizontal bars, respectively.

Figure 4

Representative actograms (left), periodograms (middle), and mean waveforms (right) obtained analyzing locomotor activity rhythms at P180 in P23H and SD × LE rats without treatment. The light/dark cycle is represented by white and dark horizontal bars, respectively.

Figure 5

Representative actograms (left), periodograms (middle), and mean waveforms (right) obtained analyzing core-body temperature rhythms at P180 in P23H and SD × LE rats with epigallocatequin gallate (EGCG) treatment. The light/dark cycle is represented by white and dark horizontal bars, respectively.

Figure 6

Representative actograms (left), periodograms (middle), and mean waveforms (right) obtained analyzing locomotor activity rhythms at P180 in P23H and SD × LE rats with epigallocatequin gallate (EGCG) treatment. The light/dark cycle is represented by white and dark horizontal bars, respectively.

Figure 7

Levels of (a) malondialdehyde and 4-hidroxyalkenals (MDA and 4-had, respectively), (b) oxidized proteins (protein carbonyl groups), (c) nitrosative damage (nitrite levels), and (d) the ratio of reduced and oxidized glutathione (GSH/GSSG) in the liver of P23H and SD × LE treatment groups. Epigallocatequin gallate (EGCG). Data represent the mean ± standard error (n = 5 per group). Mann–Whitney U test, * p < 0.05 versus P23H-vehicle animals, # p < 0.05 versus SD × LE animals.

Figure 8

Levels of (a) total antioxidant capacity (TAC), (b) catalase (CAT), (c) superoxide dismutase (SOD), and (d) glutathione S-transferase (GST) activity in P23H rats’ livers and SD × LE treatment groups. Epigallocatequin gallate (EGCG). Data are represented as the mean ± standard error (n = 5 per group). Mann–Whitney U test, * p < 0.05 versus P23H-vehicle animals, # p < 0.05 versus SD × LE animals.