Vitamin A and vitamin D3 protect the visual apparatus during the development of dopamine-2 receptor knockout mouse model of Parkinsonism

Abstract

Abstract Objectives Dopamine-related movement disorders are associated with a loss of visual acuity. Studies have shown that chemical stimulation of the vitamin D3 receptor (VDR) ameliorates movement disorders; however, the chemical stimulation is not effective when there is a deficiency of vitamin A in the cells. In the study, we examine the role of VDR and its interplay with vitamin A in impaired visual function in the dopamine deficit model. Methods Thirty (30) male mice with an average weight of 26 g ± (2) were divided into six group (NS,−D2,−D2 + VD D2 + VD, −D2 + VA, −D2 + (VD + VA) and −D2 + D2 groups). Dopamine deficit models of movement disorders were created using 15 mg/kg of haloperidol (−D2) injected intraperitoneally daily for 21 days. In the −D2 + (VD + VA) group, 800 IU/day of vitamin D3 (VD) and 1000 IU/day of vitamin A were concurrently used, while in the −D2 + D2 group, bromocriptine (+D2) was used as the standard treatment of the model. At the end of the treatment phase, the animals were subjected to visual water box test for visual acuity. The level of oxidative stress was measured using Superoxide dismutase (SOD) and malondialdehyde (MDA) in the retina and visual cortex. The level of cytotoxicity in these tissues was measured using Lactate dehydrogenase (LDH) assay, while the structural integrity of these tissues was assessed using a light microscope by assessing slide mounted sections that were stained with haematoxylin and eosin. Results A significant decline in time taken to reach the escape platform in the visual water box test was observed in the −D2 (p<0.005) and −D2 + D2 (p<0.05) group. In the retina and the visual cortex, a significant increase in LDH, MDA and the density of degenerating neurons was observed in the −D2 and −D2 + D2 groups. LDH level in the retina was also found to be significantly increased in (−D2 + VD, −D2 + VA, −D2 + (VD + VA). A Significant decrease in SOD was found in the retina and visual cortex of −D2 and −D2 + D2 group. In the histology of the retina, thinning of the retina, retinal fold, distortion and retinal detachment were all seen in the −D2 group. These structural alterations were not seen in other groups. Histological hallmarks of degeneration were observed in the visual cortex of the mice from the −D2 (p<0.001), −D2 + D2 (p<0.005) and −D2 + VD (p<0.05) groups only. Conclusions Dopamine-deficient models of movement disorders are associated with loss of visual functions, especially due to thinning of the retina, retinal fold, retinal detachment, and neurodegeneration in the visual cortex. Supplementation during the development of the model with vitamin D3 and vitamin A prevented the deterioration of the retina and visual cortex by reducing the degree of oxidative stress and cytotoxicity.