Abstract
Purpose:
To study the neuroprotective effect of thymoquinone in ameliorating the retinal damage caused by intravitreal rotenone in a rat model of Leber’s hereditary optic neuropathy.
Methods:
Sprague-Dawley rats were treated with daily intraperitoneal injection of thymoquinone ((2mg/kg or 5mg/kg), or vehicle for 9 consecutive days (n=5 per group). On day 3, the rats received either intravitreal rotenone (5μm) or vehicle (0.1% DMSO) injection in the left eye. On day 10, the retinal tissues were harvested, fixed and processed for haemotoxylin and eosin (H&E) staining and immunohistochemistry. Retinal thickness was measured based on H&E retinal staining. Immunofluorescence staining was performed using GFAP and Brn3a antibodies.
Results:
Rotenone caused 33% retinal thinning (p<0.001) with a mean retinal thickness of 105.19±0.59μm compared to 154.46±2.74μm in controls (vehicle). Thymoquinone significantly ameliorated rotenone-induced retinal thinning at both concentrations used 2mg/kg dosing: 13% thinning, p=0.03; 5mg/kg dosing: 3% thinning, p=0.0058. Daily intraperitoneal thymoquinone intraperitoneal of 5mg/kg dosing almost completely reversed the effects of rotenone, causing structural preservation of 95% of retinal thickness (mean retinal thickness of 148.85±0.65μm), compared to 67% residual retinal thickness as a result of rotenone damage.
Conclusions:
This study showed thymoquinone significantly preserves structural intergrity of the retina and attenuates retinal thinning caused by rotenone based on histological and immunofluorescence studies. The results suggests that thymoquinone may act as a strong neuroprotective agent in the retina, specifically against complex I inhibition of a rat model of Leber’s hereditary optic neuropathy.