Magnesium is one of the most important regulatory cation involved in several biological processes. It is important for maintaining the structural and functional integrity of several vital ocular tissues such as cornea, lens and retina. The magnesium content of lens, especially in its peripheral part, is higher than that in aqueous and vitreous humor. Magnesium has also been shown to play critically important role in retinal functions. Magnesium plays significant role as a cofactor for more than 350 enzymes in the body and regulates neuroexcitability and several ion channels. Membrane associated ATPase functions that are crucial in regulating the intracellular ionic environment, are magnesium-dependent. Moreover, the enzymes involved in ATP production and hydrolysis are also magnesium-dependent. Magnesium deficiency by interfering with ATPase functions causes increased intracellular calcium and sodium and decreases intracellular potassium concentration. Such ionic imbalances in turn alter the other cellular enzymatic reactions and form the basis of the association of magnesium deficiency with ophthalmic diseases such as cataract. In presence of magnesium deficiency, an imbalance between mediators of vasoconstriction and vasorelaxation may underlie the vasospasm, which is one of the pathogenic factors in primary open angle glaucoma. Furthermore, magnesium deficiency is also a contributing factor in increased oxidative stress and inducible NOS stimulation that can further contribute in the initiation and progression of ocular pathologies such as cataract, glaucoma and diabetic retinopathy. In this paper we review the association of disturbances of magnesium homeostasis with several ophthalmic diseases.
Cataract, a leading cause of blindness, is characterized by lenticular opacities resulting from denaturation of lens proteins due to activation of calcium-dependent enzyme, calpain. Magnesium (Mg(2+)) plays an important role not only in maintaining a low lenticular calcium (Ca(2+)) and sodium concentration but also in preserving the lens redox status. Taurine has also been shown to reduce lenticular oxidative stress. Present study evaluated the anticataract effects of magnesium taurate in vivo and in vitro. Among the five groups of 9 Sprague Dawley rats each, two groups received 30% galactose diet with topical (GDMT) or oral treatment (GDMO) with magnesium taurate. Two groups received 30% galactose diet with topical (GDT) or oral vehicle (GDO). Remaining 1 group received normal diet (ND). Weekly slit lamp examination was done during 21 days experimental period and then all rats were sacrificed; Ca/Mg ratio and antioxidant parameters including reduced glutathione (GSH), catalase and superoxide dismutase (SOD) activities were measured in the isolated lenses using ELISA. In the in vitro study, 2 groups of 10 normal rat lenses were incubated in Dulbecco's Modified Eagle's Medium (DMEM) with galactose while 1 similar group was incubated in DMEM without galactose. In one of the groups, galactose containing medium was supplemented with magnesium taurate. After 48 h of incubation, lenses were photographed and Ca(2+)/Mg(2+) ratio and antioxidant parameters were measured as for in vivo study. The in vivo study, at the end of experimental period, demonstrated delay in the development of cataract with a mean opacity index of 0.53 ± 0.04 and 0.51 ± 0.03 in GDMO (p < 0.05 versus GDO) and GDMT (p < 0.01 versus GDT) respectively. Histopathological grading showed a lower mean value in treated groups, however, the differences from corresponding controls were not significant. Lenticular Ca(2+)/Mg(2+) ratio with a mean value of 1.20 ± 0.26 and 1.05 ± 0.26 in GDMO and GDMT was significantly lower than corresponding controls (p < 0.05) and in GDMT no significant difference was observed from ND. Lenticular GSH and catalase activities were significantly lower and SOD activity was significantly higher in all galactose fed groups. However, in GDMT, GSH and catalase were significantly higher than corresponding control with mean values of 0.96 ± 0.30 μmol/gm lens weight and 56.98 ± 9.86 μmol/g lens protein respectively (p < 0.05 for GSH and p < 0.01 for catalase). SOD activity with mean values of 13.05 ± 6.35 and 13.27 ± 7.61 units/mg lens protein in GDMO and GDMT respectively was significantly lower compared to corresponding controls (p < 0.05) signifying lesser upregulation of SOD due to lesser oxidative stress in treated groups. In the in vitro study, lenses incubated in magnesium taurate containing medium showed less opacity and a lower mean Ca(2+)/Mg(2+) ratio of 1.64 ± 0.03, which was not significantly different from lenses incubated in DMEM without galactose. Lens GSH and catalase activities were restored to normal in lenses incubated in magnesium taurate containing medium. Both in vivo and in vitro studies demonstrated that treatment with magnesium taurate delays the onset and progression of cataract in galactose fed rats by restoring the lens Ca(2+)/Mg(2+) ratio and lens redox status.
The study aimed to determine current status of knowledge, practices, and attitudes towards adverse drug reaction (ADR) reporting among private practitioners in Klang region of Malaysia.
Senile cataract is the most common cause of bilateral blindness and results from the loss of transparency of the lens. Maintenance of the unique tissue architecture of the lens is vital for keeping the lens transparent. Membrane transport mechanisms utilizing several magnesium (Mg)-dependent ATPases, play an important role in maintaining lens homeostasis. Therefore, in Mg-deficiency states, ATPase dysfunctions lead to intracellular depletion of K(+) and accumulation of Na(+) and Ca(2+). High intracellular Ca(2+) causes activation of the enzyme calpain II, which leads to the denaturation of crystallin, the soluble lens protein required for maintaining the transparency of the lens. Mg deficiency also interferes with ATPase functions by causing cellular ATP depletion. Furthermore, Mg deficiency enhances lenticular oxidative stress by increased production of free radicals and depletion of antioxidant defenses. Therefore, Mg supplementation may be of therapeutic value in preventing the onset and progression of cataracts in conditions associated with Mg deficiency.
Magnesium is one of the most important regulatory cation involved in several biological processes. It is important for maintaining the structural and functional integrity of vital ocular tissues such as lens. Presence of high magnesium content especially in the peripheral part of lens as compared to aqueous and vitreous humor has been observed. Magnesium plays significant role as a cofactor for more than 350 enzymes in the body especially those utilizing ATP. Membrane associated ATPase functions that are crucial in regulating the intracellular ionic environment, are magnesium-dependent. Moreover, the enzymes involved in ATP production and hydrolysis are also magnesium-dependent. Magnesium deficiency by interfering with ATPase functions causes increased intracellular calcium and sodium and decreases intracellular potassium concentration. Furthermore, magnesium deficiency is associated with increased oxidative stress secondary to increased expression of inducible nitric oxide synthase and increased production of nitric oxide. Thus the alterations in lenticular redox status and ionic imbalances form the basis of the association of magnesium deficiency with cataract. In this paper we review the mechanisms involved in magnesium homeostasis and the role of magnesium deficiency in the pathogenesis of cataract.
Glaucoma, a neurodegenerative disease, is currently being treated by modulation of one of its primary risk factors, the elevated intraocular pressure. Newer therapies that can provide direct neuroprotection to retinal ganglion cells are being extensively investigated. Tumor necrosis factor-α, a cytokine, has been recognized to play an important role in pro and antiapoptotic cellular events. In this paper we review the relevant literature to understand (1) The association of increased expression of tumor necrosis factor-α with glaucomatous neurodegeneraion, (2) Modulation of tumor necrosis factor-α expression by exposure to various risk factors of glaucoma, (3) Downstream cellular signaling mechanisms following interaction of tumor necrosis factor-α with its receptors and (4) Role of tumor necrosis factor-α as a possible target for therapeutic intervention in glaucoma. Literature was reviewed using PubMed search engine with relevant key words and a total of 82 English language papers published from 1990 to 2010 are included in this review.
Glaucoma, a leading cause of irreversible blindness, is often associated with increased resistance to aqueous outflow in trabecular tissue. Increased outflow resistance has been attributed to increased extracellular matrix (ECM) deposition in trabecular tissue. A critical balance between the synthesis and breakdown of the components of extracellular tissue is important in keeping the intraocular pressure within the normal range. Multiple mechanisms have been shown to affect ECM turnover in trabecular tissue. In this review, we examine the related literature to understand the role of TGF-beta in ECM turnover, in the development and progression of glaucoma, and in possible therapeutic strategies that can be devised by targeting the TGF-beta signaling pathways.
Curcuma longa is among the most commonly used spices in India and other Asian countries. The herb has also been used in Ayurveda and other traditional systems of medicine for the prevention and treatment of a variety of ailments. Curcuminoids are the major chemical constituents of C. longa that are of medicinal importance. Today, a large body of scientific evidence exists to indicate potential therapeutic benefits of C. longa. Several preclinical and clinical studies have investigated the pharmacological properties of C. longa and results indicate strong therapeutic potential for anti-inflammatory, antioxidant, antibacterial, anticancer and many other properties.
Glaucoma, recognized as optic neuropathy is the second largest cause of blindness worldwide. The disease is characterized by progressive loss of retinal ganglion cells and visual field defects. The pathophysiological factors involved in the onset and progression of glaucoma are not fully understood. However, it is now well accepted that elevated intraocular pressure is not the only causative factor. The pathophysiology of glaucoma involves multiple factors that interact in a highly complex manner to favor development of glaucomatous optic neuropathy. As the knowledge of molecular mechanisms involved is expanding, more and more therapeutic targets are being recognized for the development of safe and effective pharmacotherapy of glaucoma. Although at present the intraocular pressure lowering drugs are still the first line of treatment, the prospect of introducing neuroprotective therapies that can directly protect and perhaps stimulate regeneration of dying and dead retinal ganglion cells, shows considerable promise. This review presents recent developments in the pathophysiology and pharmacotherapy of glaucoma.