Amlodipine Attenuates Carrageenan-induced Oxidative Stress Targeting Transsynaptic Neuronal Damage by Promoting Survival of Retinal Ganglion Cells in Adult Zebrafish (Danio rerio)

Abstract

Transsynaptic degeneration of retinal ganglion cells (RGCs) likely plays a role in progressive loss of vision in glaucoma. Carrageenan (Carr), obtained from seaweed (Rhodophyceae), a sulphated polysaccharide extracted from a species of red algae ( Chondrus crispus), is a reversible gel mostly used in eye-drop preparation due to its hydrocolloid nature. But Carr-induced inflammation causing oxidative stress in animals has not yet been evaluated. It was reported that amlodipine (AML) can inhibit inflammatory cytokines by lowering intracellular calcium concentration and increasing antioxidant defences. In this study, we examined the impact of AML administration on Carr-induced oxidative stress, causing free radial–mediated neurodegeneration and behavioural alteration in zebrafish. We aimed to evaluate the behavioural alteration in zebrafish using the novel tank diving test (NTDT) and the light-dark preference test (LDPT) as invaluable tools for analysing visual functions. To understand the role of the antioxidant defence system, oxidative stress biomarkers such as lipid peroxidation and CAT activity were analysed. RGCs of the retina of the eye and neurons of the optical tectum (TeO) in the brain were investigated by histopathological studies. Carr-treated groups swam in random patterns and showed an increased number of transitions and spent more time in alter zones, whereas controls prefer perceived motion. AML significantly attenuates the increased lipid peroxidation level and decreased CAT activity with Carr administration. Histopathological analysis showed an increase in the percentage of pyknotic cell counts after Carr treatment, whereas AML supplementation significantly reduced the pyknotic RGC cell count in the retina and TeO of the brain. Findings showed the effectiveness of AML as an antioxidant and neuroprotective agent by reducing pyckonsis in developmental RGCs and possible repair mechanisms against Carr-induced oxidative stress. This study may be useful to know the underlying mechanisms of weakening and eliminating central neurons for synaptic connections in the visual system of zebrafish.