CHAPTER ONE
1.0 INTRODUCTION
Glaucoma is an optic neuropathy that causes progressive changes in the visual field and whose main known sick factor is the increased intraocular pressure (Osborne 2008). Glaucoma is the second leading cause of blindness in the world, affecting about five million people (Foster et al., 2006), and it is the leading cause of blindness in Japan (Iwaseetal., 2006). Glaucoma is classified into 2 types; the primary open – angle glaucoma (POAG) and the closed angle glaucoma (Osborne, 2008). The primary open angle glaucoma (POAG) is associated with asymptomatic and irreversible vision loss, although it cause is unknown, it is known that in the presence elevated intra-ocular pressure (IOP) occurs sequentially death of retinal ganglion cells by apoptosis and optic neural fibers in its evolution cause of glaucomatous optic atrophy and permanent loss of vision (Osborne, 2008). There is evidence in the field of health that there is a connection between oxidative stress and glaucoma (Kong et al., 2009). Oxidative stress is essentially the imbalance between the productions of free radicals and the ability of the body to counteract or detoxify their harmful effects through neutralization by anti-oxidants (Tezel, 2006).We know that stress causes oxidative damage to biomolecules, especially lipids, nucleic acids, proteins and the oxidative destruction or damage of this lipid is known as lipid perioxidation (Izzottiet al., 2006).Lipid perioxidation is the oxidative degradation of lipids. It is the process in which free radicals “steal” electrons from the lipids in cell membrane, resulting in cell damage and this process proceeds by a free radical chain reaction mechanism. It most often affects polyunsaturated fatty acids, they contain multiple double bonds in between i.e. methylene bridges [-CH2] that posses especially reactive hydrogen atoms (Izzotiet al., 2006). With any radical reaction (Guptonet al., 2017). Tissue damage due to oxidation is a chain reaction, which is mainly initiated by the production of free oxygen radicals. Though these molecules interact with intracellular signal conduction and regulation mechanisms, they demonstrate their main effect as destructive changes induced by a series of DNA reactions and macromolecules, such as lipids (Tezel, 2006). Oxidation degradation products which are tissue and serum markers of this destructive process, consists of malonlydialdehyde (MDA), (Kalousoraet al., 2011). Vitamin E, C, and A, molecule like homocysteine, and transfer bind oxygen ions and transform into steady –state compounds with their resultant antioxidants effect. Serine (SER) is an amino acid used in the effect pathway of vitamin E. these buffer compounds that are formed offer their ions to the down regulating (velocity limiting) systems, which consist of superoxide dismutase (SOD) and glutathione perioxidase (GPX) to curtail chain reactions (Elliot et al., 2009) .The nervous system which also includes retina ganglion cells is rich in lipids. Further the metabolic rate, oxygen degradation and synthesis of ATP are increased in the cells, while the cellular regeneration rate is restricted. Dopamine oxidation and chemical factors e.g. Glutamate, are also important. Secondary to all of these factors, nerve cells are quite sensitive to oxidative damage (Tezel, 2006). The use of antioxidants for the prevention of glaucomatous decay is also saddressed. Higher lipids content of the nerve cells has also enhanced the importance of lipids. Soluble vitamin E, especially – tocopherol, which has hormone like regulatory mechanism with its unique transporter receptors, exerting neurol modulatory effects on the eye and other tissues.Neuroprotective effects of vitamin E compounds in retinal diseases and glaucoma have been clinically demonstrated (Engin, 2009). Vitamin A is a group of unsaturated nutritional organic compounds that includes retinol, retinal, retinoic acid, and several provitamin A carotenoids (most notably beta-carotene), (Fennema and Owen, 2008). Vitamin A has multiple functions: it is important for growth and development, for the maintenance of the immune system and good vision (Tanumihardjo, 2011). Vitamin A is needed by the retina of the eye in the form of retinal, which combines with protein opsin to form rhodopsin, the light-absorbing molecule (Wolf, 2001) necessary for both low-light (scotopic vision) and color vision. Vitamin A also functions in a very different role as retinoic acid (an irreversibly oxidized form of retinol), which is an important hormone-like growth factor for epithelial and other cells (Tanumihardjo, 2011). Vitamin C is a monosaccharide oxidation-reduction (redox) catalyst found in both animals and plants. As one of the enzymes needed to make ascorbic acid has been lost by mutation during primateHYPERLINK “https://en.wikipedia.org/wiki/Primate”evolution, humans must obtain it from the diet; it is therefore a vitamin (Smirnoff, 2001). Most other animals are able to produce this compound in their bodies and do not require it in their diets (Linsteret al., 2007). Ascorbic acid is required for the conversion of the procollagen to collagen by oxidizing proline residues to hydroxyproline. In other cells, it is maintained in its reduced form by reaction with glutathione, which can be catalysed by protein disulfide HYPERLINK “https://en.wikipedia.org/wiki/Protein_disulfide_isomerase”isomerase and glutaredoxins (Meister, 1994; Wells et al., 1990). Ascorbic acid is a redox catalyst which can reduce, and thereby neutralize, reactive oxygen species such as hydrogen peroxide (Padayattyet al., 2003). In addition to its direct antioxidant effects, ascorbic acid is also a substrate for the redox enzyme ascorbateHYPERLINK “https://en.wikipedia.org/wiki/Ascorbate_peroxidase”HYPERLINK “https://en.wikipedia.org/wiki/Ascorbate_peroxidase”peroxidase, a function that is particularly important in stress resistance in plants (Shigeokaet al., 2002). Ascorbic acid is present at high levels in all parts of plants and can reach concentrations of 20 millimolar in chloroplasts (Smirnoff and Wheeler, 2000). Vitamin E is the collective name for a set of eight related tocopherols and tocotrienols, which are fat-soluble vitamins with antioxidant properties (Herrera and Barbas, 2001; Packer et al., 2001). Of these, α-tocopherolhas been most studied as it has the highest bioavailability, with the body preferentially absorbing and metabolising this form (Brigelius and Traber, 1999). It has been claimed that the α-tocopherol form is the most important lipid-soluble antioxidant, and that it protects membranes from oxidation by reacting with lipid radicals produced in the lipid peroxidation chain reaction (Herrera and Barbas, 2001; Traber and Atkinson, 2007). This removes the free radical intermediates and prevents the propagation reaction from continuing. This reaction produces oxidised α-tocopheroxyl radicals that can be recycled back to the active reduced form through reduction by other antioxidants, such as ascorbate, retinol or ubiquinol (Wang and Quinn, 1999). This is in line with findings showing that α-tocopherol, but not water-soluble antioxidants, efficiently protects glutathione peroxidase 4 (GPX4)-deficient cells from cell death (Seiler et al., 2008). GPx4 is the only known enzyme that efficiently reduces lipid-hydroperoxides within biological membranes.However, the roles and importance of the various forms of vitamin E are presently unclear, (Brigelius and Davies, 2007; Atkinson et al., 2008), and it has even been suggested that the most important function of α-tocopherol is as a signaling molecule, with this molecule having no significant role in antioxidant metabolism ( Zingg and Azzi, 2004). The functions of the other forms of vitamin E are even less well understood, although γ-tocopherol is a nucleophile that may react with electrophilic mutagens, (Brigelius and Traber, 1999) and tocotrienols may be important in protecting neurons from damage (Senet al., 2006).
1.1 JUSTIFICATON
The eye is a complex organ which reacts to light and pressure. As a sense organ, the mammalian eye allows vision. Glaucoma is a disease that occurs as a result of the increase in the fluid pressure within the eyes. This eye disease can lead to blindness if left untreated in a patient. The level of glaucoma or its occurrence in people is becoming outrageous in the study area and has become a public health problem. It is the most common cause of blindness worldwide and in Nigeria with a prevalence of 16.7% apart from it heritable nature (Seiler et al., 2008). It does not only occur in ageing people but also in children with different symptoms and signs leading to vision loss. Apart from inheritance, the causes and etiologic factors of glaucoma remains a mystery. Oxidative stress has been implicated as one of the etiologic factors. It becomes necessary therefore to assess the levels of these markers of oxidative stress in glaucoma patients to actually ascertain the role of stress in the pathophysiology of this dangerous disease.
1.2 AIM
The aim of this study is to determine Malondaldehyde (MDA), Antioxidant vitamins A, C and E of some patients with glaucoma in Owerri, Imo state.
1.3 OBJECTIVES
- To determine the levels of the product of lipid peroxidation MDA in patients with glaucoma
- To determine the levels of some markers of oxidative stress viz vitamins A, C and E in patients with glaucoma
To compare the levels of MDA, vitamins A, C and E in some apparently healthy subjects with those of the patients with glaucoma.
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