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  1. Agarwal R, Iezhitsa IN, Agarwal P, Spasov AA
    Magnes Res, 2013 Jan-Feb;26(1):2-8.
    PMID: 23708888 DOI: 10.1684/mrh.2013.0336
    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.
    Matched MeSH terms: Cataract/pathology
  2. Syafruddin SE, Ling S, Low TY, Mohtar MA
    Biomolecules, 2021 Mar 31;11(4).
    PMID: 33807297 DOI: 10.3390/biom11040523
    Cells encounter a myriad of endogenous and exogenous stresses that could perturb cellular physiological processes. Therefore, cells are equipped with several adaptive and stress-response machinery to overcome and survive these insults. One such machinery is the heat shock response (HSR) program that is governed by the heat shock factors (HSFs) family in response towards elevated temperature, free radicals, oxidants, and heavy metals. HSF4 is a member of this HSFs family that could exist in two predominant isoforms, either the transcriptional repressor HSFa or transcriptional activator HSF4b. HSF4 is constitutively active due to the lack of oligomerization negative regulator domain. HSF4 has been demonstrated to play roles in several physiological processes and not only limited to regulating the classical heat shock- or stress-responsive transcriptional programs. In this review, we will revisit and delineate the recent updates on HSF4 molecular properties. We also comprehensively discuss the roles of HSF4 in health and diseases, particularly in lens cell development, cataract formation, and cancer pathogenesis. Finally, we will posit the potential direction of HSF4 future research that could enhance our knowledge on HSF4 molecular networks as well as physiological and pathophysiological functions.
    Matched MeSH terms: Cataract/pathology*
  3. Iezhitsa I, Agarwal R, Saad SD, Zakaria FK, Agarwal P, Krasilnikova A, et al.
    Mol Vis, 2016;22:734-47.
    PMID: 27440992
    PURPOSE: Increased lenticular oxidative stress and altered calcium/magnesium (Ca/Mg) homeostasis underlie cataractogenesis. We developed a liposomal formulation of magnesium taurate (MgT) and studied its effects on Ca/Mg homeostasis and lenticular oxidative and nitrosative stress in galactose-fed rats.

    METHODS: The galactose-fed rats were topically treated with liposomal MgT (LMgT), liposomal taurine (LTau), or corresponding vehicles twice daily for 28 days with weekly anterior segment imaging. At the end of the experimental period, the lenses were removed and subjected to analysis for oxidative and nitrosative stress, Ca and Mg levels, ATP content, Ca(2+)-ATPase, Na(+),K(+)-ATPase, and calpain II activities.

    RESULTS: The LTau and LMgT groups showed significantly lower opacity index values at all time points compared to the corresponding vehicle groups (p<0.001). However, the opacity index in the LMgT group was lower than that in the LTau group (p<0.05). Significantly reduced oxidative and nitrosative stress was observed in the LTau and LMgT groups. The lens Ca/Mg ratio in LMgT group was decreased by 1.15 times compared to that in the LVh group. Calpain II activity in the LMgT group was decreased by 13% compared to the LVh group. The ATP level and Na(+),K(+)-ATPase and Ca(2+)-ATPase activities were significantly increased in the LMgT group compared to the LVh group (p<0.05).

    CONCLUSIONS: Topical liposomal MgT delays cataractogenesis in galactose-fed rats by maintaining the lens mineral homeostasis and reducing lenticular oxidative and nitrosative stress.

    Matched MeSH terms: Cataract/pathology
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