Amlodipine protects the retinal ganglionic cell damage maintaining intra ocular pressure by regulating the biological activities of carrageenan like red algae: an in vivo and in-silico study

Carrageenan (Carr), a natural polysaccharide derived from edible red algae, was used for the green biosynthesis and also recognized as toxic compound causing oxidative stress. The objective was to know the insight mechanism of Carr-induced retino ganglionic cell (RGCs) damage and its connection with brain having two model systems, mammalian (rabbit), lower vertebrates (zebrafish). The present study investigated the modulatory effect of amlodipine (AML), a dihydropyridine calcium channel antagonist, against Carr-induced RGCs loss. AML and Carr were analyzed through in silico study to predict their protein targets and infer their drug-target interactions with glaucoma. AML demonstrated strong binding affinity with differentially expressed glaucoma targets of Carr, specifically N-formyl peptide receptor, N-type calcium channel and sodium channel protein type, suggesting a clue towards the link with the regulatory role of AML. The neuronal damage in RGCs layer was clearly observed through histopathological study in Carr-treated zebrafish while amlodipine co-administration with Carr shown to decrease the percentage of pycknotic cell count in zebrafish brain. A 40% decrease in IOP was observed after exposure to topical AML in the normotensive rabbit eye after carrageenan treatment, with IOP returning to baseline by 300 min. In conclusion, the present study involving in silico and in vivo analysis demonstrated that AML has protective role against carr-induced oxidative stress promoting RGC degeneration with IOP lowering property. Identification of AML like pharmacologic modulators is needed to develop new therapeutic targets for visual system disorders.