Abstract
Glaucoma has engulfed a huge population of the world into its claws of blindness as it remains asymptomatic until nearly 40% of the neurons are lost and the only option left is for patients to be subjected to symptomatic treatments or surgical methods, neither of which is completely effective in curing the disease as they do not restore the physiological dimensions at the neuronal level. Among the several factors that drive the pathophysiology of glaucoma, one is the involvement of fibrogenic factors, such as transforming growth factor β (TGFβ) which remodels the extracellular matrix (ECM) and, thus, the deposition of fibrotic material in the retina, resulting in the progression of primary open-angle glaucoma (POAG). The primary objectives of this study were to evaluate the protective effects of oxymatrine (OMT) in the steroid-induced glaucoma model in experimental rats and to determine the role of transforming growth factor β1 (TGFβ1) in the pathogenesis of glaucoma and its consequent inhibition due to the antioxidant and the antiinflammatory, and also the TGFβ1 antagonistic, behavior of OMT. To that end, we experimentally elucidated the role of OMT, a TGFβ1 antagonist, that is known to play antiinflammatory and antioxidant roles in the steroid-induced glaucoma model in experimental rats, and using the enzyme-linked immunosorbent assay (ELISA), we observed a direct inhibitory effect of OMT on the pathogenesis of glaucoma. The antioxidant and the antiinflammatory potentials of OMT were determined using several biochemical methods to determine the major antioxidants in the retinal layers, such as superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT), and glutathione (GSH), along with the nitrite and the malondialdehyde (MDA) concentration levels. As a result, OMT was found to reduce the total protein content in the retinal layers, a correlation that has not been previously reported. Moreover, the impacts of OMT on the major governing ATPases, namely Na+/K+ ATPase and Ca2+ATPase, along with its impacts on the intracellular ionic concentrations of Na+, K+, and Ca2+, were determined and were found to point toward OMT, restoring homeostasis in glaucomatous animals. A clearer picture of the changes during the treatment was obtained using retinal images of the live animals and of the lenticular changes in the sacrificed animal; these images provided data on the pathological pathways leading to glaucoma inception and its consequent inhibition by OMT. The data reported in this study clearly indicate that OMT has a possible role in inhibiting the pathogenesis of glaucoma, and the data also permit the quantification of several biochemical parameters of concern.
Highlights
Fibrotic disorders have been of increasing concern in the domain of ocular disorders, and the transforming growth factor β (TGFβ) plays a pivotal role in their progression
Even though a variety of experimental findings have demonstrated the effective contribution of transforming growth factor β2 (TGFβ2) in patients with glaucoma, the relationship between glaucoma and TGFβ1 has needed further investigation, which has led to the use of OMT, a TGFβ1 antagonist extracted from the roots of Sophora flavescens Ait, belonging to the family Fabaceae and a known savior for patients with fibrotic diseases [12,13,14]
Two weeks of OMT administration at a dose of 50 μl of 0.25% OMT led to significant increases in some of the antioxidant levels, such as CAT (p < 0.001, p < 0.001, p < 0.001) and SOD (p < 0.001, p < 0.01, p < 0.001) when compared to the normal, glaucoma control, and standard groups, respectively, GPx (p < 0.001, p < 0.001) when compared to the glaucoma control and the standard groups, respectively, and GSH (p < 0.001, p < 0.001) when compared to the normal and standard groups, respectively, but with no significant variations from the glaucoma control group
Summary
Fibrotic disorders have been of increasing concern in the domain of ocular disorders, and the transforming growth factor β (TGFβ) plays a pivotal role in their progression. This multifunctional cytokine has been found to have a strong impact on the deposition and the expression of the extracellular matrix (ECM) and has been observed to be increased in aqueous humor (AH) and reactive optic nerve astrocytes of patients with primary openangle glaucoma (POAG). Even though a variety of experimental findings have demonstrated the effective contribution of TGFβ2 in patients with glaucoma, the relationship between glaucoma and TGFβ1 has needed further investigation, which has led to the use of OMT, a TGFβ1 antagonist extracted from the roots of Sophora flavescens Ait, belonging to the family Fabaceae and a known savior for patients with fibrotic diseases [12,13,14]
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