These are just a collection of statements and studies I found while researching alpha-1-antitrypsin deficiency (A1AT) and it's relationship to decreased levels of glutathione. Doing this, I found there's also a relationship b/w A1AT, corneal problems and antioxidants. I've also been reading into improving conditions like myopia and astigmatism and found some studies that make important implications.
Supplements discussed: Magnesium, Zinc, NAC, Glisodin, Vitamin E, Pycnogenol, Taurine. I omitted vitamin A, Lutein and the "xathins" as these have already been discussed in this board but are just as important.
Zinc and Myopia
>Myopia is a refractive error where there is antero-posterior elongation of the orbit causing light to focus in front of the retina.
Prevention of axial elongation in myopia by the trace element zinc.
The effect of the trace element zinc on the change in the axial length and diopters and the variations of activities of superoxide dismutase (SOD) and nitric oxide synthase (NOS), and the content of NO in the retino pigmental epithelium choroid homogenate of the myopic eyes in form-sense-deprived chicks were studied. The results show that zinc can inhibit the elongation of axis oculi and increase the diopters in myopia. Meanwhile, the activities of SOD and NOS and the content of NO are significantly increased compared with the model group, indicating that zinc can be used to prevent and treat myopia to a certain extent.
>SOD is increased in myopia---> increased oxidative stress? Why??
Effects of zinc and copper metabolism in highly myopic patients.
There is considerable evidence supporting a link between abnormalities in zinc and copper metabolism and some disorders of the retinal pigment epithelium. Anatomical studies in highly myopic eyes show important changes in this retinal layer. We measured the blood concentrations of zinc and copper and the urine concentration of copper in different groups of highly myopic patients from Caucasian and African populations, and in highly myopic patients with retinal detachment. In the Caucasian myopic groups, many patients showed high levels of zinc and low levels of copper in serum. In the high myopic group with retinal detachment, serum zinc and copper concentrations were significantly elevated. The importance of our findings and their connection to the retinal pigment epithelium is discussed.
>Can anyone access this study? Is copper/zinc low or not being used by cells for connective tissue repair? Is it high, being pro-oxidant and activating metalloproteinases and destroying connective tissue?
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Keratoconus and Magnesium
The possible relationship between keratoconus and magnesium deficiency.
The cause of keratoconus is unknown. However, an earlier report demonstrated magnesium deficiency in keratoconus patients, and suggested that magnesium deficiency could pathologically affect the mechanisms of the cornea. Experimental and clinical papers concerning a possible relationship between keratoconus and magnesium deficiency were reviewed. These studies have demonstrated molecular and cellular alterations specific to the keratoconic cornea, including: thinning and fragmentation of membranes, degenerated cells and collagen fibres, swelling of the mitochondria, and biochemical abnormalities in protein synthesis. Similar alterations have reportedly been induced by magnesium deficiency. This review suggests a possible relationship between the specific keratoconic disorders and the alteration induced by magnesium deficiency at the intracellular and extracellular levels. Although the etiology of keratoconus is still unknown, this paper may give some new ideas for further experimental and clinical studies on the etiology of keratoconus.
>Astigmatism is considered the early beginnings of keratoconus since they both involve corneal changes. Magnesium has therapeutic implications here as well.
>The vitreous humor is composed of water and hyaluronic acid among other things. Hyaluronic acid formation is dependent, in part, on magnesium and zinc. Intraocular pressure is maintained between 10-20 mm Hg by a combination of Vitreous humor production and drainage. I am magnesium deficient. My intraocular pressure is 6 in the left eye and 10 in the right eye. Both are low.
Corneal changes in magnesium-deficient rats.
PURPOSE: The purpose of the current study is to investigate the cornea in magnesium (Mg) deficiency and elucidate the local function of trace elements. METHODS: After delivery, mother Wistar Kyoto rats were fed a low Mg diet containing 0.1 mg Mg/100 g diet with all other nutrients and distilled and deionized water. Infant rats were suckled by their mothers for 21 days and then fed the same Mg-deficient diet. Control mother rats were fed commercial rat pellets containing 24 mg Mg/100 g diet and all other nutrients. The corneas were examined by electron microscopy at 6 weeks of age. RESULTS: In the Mg-deficient rats, serum Mg levels were significantly lower and calcium (Ca) levels higher than in the control rats. The corneas of Mg-deficient rats showed decreased microvilli and microplicae in the epithelial cells of the most superficial layer, increased mitochondria with abnormal shapes in the basal cells in the epithelium, condensed chromatin in the nuclei of the basal cells, and high density deposits and macrophage-like cells in the subepithelium of the stroma. Mg-deficient rats had pentagonal and square endothelial cells. CONCLUSION: Since Mg2+ has biologic functions including structural stabilization of protein, nucleic acids, and cell membranes, Mg deficiency may induce changes in the corneal surface and nuclei of corneal epithelial and endothelial cells. These disturbances may interfere with protection from infections, foreign bodies, dryness, and direct exposure to air. Thus, Mg is essential for the cornea to maintain normal structure and function.
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http://www.opticiano...spx?ItemID=2103 (Great site for anything eye-related)
"Keratocononus, is a degenerative, non-inflammatory disorder of the cornea. It is characterised by central and para-central corneal stromal thinning and subsequent conical ectasia. This conical distortion of the cornea results in irregular astigmatism with associated reduction in visual performance. It typically presents in adolescence and progresses in a variable manner."
"The occurrence of keratoconus is usually an isolated condition, but it has been reported to occur with increased frequency in a number of ocular and systemic disorders.. Ocular associations include vernal disease, retinitis pigmentosa, blue sclera, aniridia, ectopia lentis and Leber’s congenital amaurosis. Systemic associations include atopy, magnesium deficiency, Down’s syndrome, Turner syndrome, connective tissue disorders (such as Marfan’s, Ehlers-Danlos, osteogenesis imperfecta and pseuodoxanthoma elasticum), mitral valve prolapse, Laurence-Moon-Biedl syndrome, Rieger’s syndrome and neurofibromatosis."
"It is, therefore, likely that the development of keratoconus is the final common pathway for several different disorders."
>So, if you have keratoconus or even astigmatism, I would be searching hard for some kind of ocular or systemic problem. This also means, if you can find a way to stabilize or reverse the condition, it will also have a positive effect on the disease state.
>This is where it gets good..
"Laboratory studies have indicated that keratoconic corneas show signs of increased activity of proteinase enzymes and a reduced activity in the proteinase inhibitors found within the cornea. This imbalance between corneal metalloproteinases (MMP) and its inhibitors (tissue inhibitors of metalloproteinases or TIMPS) can reduce the various extracellular matrices and proteins within the cornea, resulting in stromal thinning and breaks in Bowman’s layer/epithelial basement membrane. Enzyme proteinase inhibitors found to be reduced in keratoconic corneas include α1-proteinase inhibitor (this is the same as alpha-1-antitypsin. A deficiency of this can be treated with NAC), α2-macroglobulin and TIMP-1.17-19 These deficits may lead to an increase in the degradative enzymes present, including cathepsins, trypsins, and MMPs, including MMP-1, MMP-2 and MMP-13.20-23 Levels of TIMP-1 are also reduced by the presence of peroxynitrate, a cytotoxic by-product from the nitric oxide pathway. As yet, the cause for this increased proteinase activity in keratoconic corneas is not known. It may be related to a state of increased oxidative stress found within the keratoconic cornea.
" It is known that as the cornea is responsible for absorbing most of the UVB light that enters the eye, it has to process the oxygen-free radicals produced. Oxygen-free radicals or reactive oxygen species (ROS) are high energy molecules that can build up and cause oxidative damage to cells by reacting with proteins, DNA and membrane phospholipids.26 In addition, ROS produce aldehydes via ROS-mediated lipid peroxidation. These aldehydes can be destructive to cells by interfering with proteins and DNA, altering signal transduction and gene expression. Normally the cornea eliminates ROS by various antioxidant enzymes, including superoxide dismutase, (SOD), catalase, glutathione reductase and glutathione peroxidise and protects itself from lipid peroxidation damage by glutathione S-transferase and aldehyde dehydrogenase enzymes (ALDH3). It has been shown that keratoconic corneas are deficient in SOD, catalase and ALDH3. These deficits may cause a significant build up in malondialdehyde (MDA) a cytotoxic aldehyde from both the lipid peroxidation and nitric oxide pathways."
>Part 2 of the article talks about treatment and it goes off in the typical profit-minded fashion using lasers and other costly, invasive procedures. It says nothing about restoring magnesium status or increasing glutathione, SOD and catalase defenses. So NAC and Glisodin have important implications here. There are more studies that support this.
Superoxide dismutase isoenzymes in the normal and diseased human cornea.
PURPOSE: The human cornea, a tissue much exposed to oxidative stress, is rich in extracellular superoxide dismutase (SOD). In this study, the contents and distributions of the SOD isoenzymes in the normal human cornea were compared with those in corneas affected by keratoconus and bullous keratopathy. METHODS: The central and peripheral parts of normal human corneas were analyzed separately. Central corneal buttons were obtained from patients with keratoconus and bullous keratopathy who were undergoing primary keratoplasty or retransplantation. SOD enzymatic activities were determined by a direct spectrophotometric method, and extracellular SOD and the cytosolic Cu- and Zn-containing SOD (CuZn-SOD) proteins were determined with ELISA and studied with immunohistochemistry. RESULTS: The total SOD content, and particularly the extracellular SOD content, was lower in the central than in the peripheral normal cornea. CuZn-SOD and extracellular SOD were demonstrated in all three corneal layers. CuZn-SOD was found in cells, whereas extracellular SOD appeared to be localized on cell surfaces, in basal membranes, and in the stroma. In keratoconus, corneal levels of extracellular SOD were half those in the control corneas, whereas CuZn-SOD and the mitochondrial Mn-containing SOD levels were normal. In bullous keratopathy, apart from edematous dilution, SOD isoenzyme levels were essentially normal. In a remarkable finding, the same pattern in SOD isoenzyme levels as in the original disease was also found at retransplantation. CONCLUSIONS: Extracellular SOD and CuZn-SOD show markedly different distribution patterns within the human cornea. Extracellular SOD activity in the central cornea is halved in keratoconus, compared with that in normal control corneas. The finding of a similar reduction at retransplantation in keratoconus suggests reduced corneal extracellular SOD synthesis in cells of the host as a cause of the low enzyme levels.
Increased levels of catalase and cathepsin V/L2 but decreased TIMP-1 in keratoconus corneas: evidence that oxidative stress plays a role in this disorder.
CONCLUSIONS: Keratoconus corneas have elevated levels of cathepsins V/L2, -B, and -G, which can stimulate hydrogen peroxide production, which, in turn, can upregulate catalase, an antioxidant enzyme. In addition, decreased TIMP-1 and increased cathepsin V/L2 levels may play a role in the matrix degradation that is a hallmark of keratoconus corneas. The findings support the hypothesis that keratoconus corneas undergo oxidative stress and tissue degradation.
Edited by Lufega, 26 July 2009 - 10:54 PM.