© Springer Science+Business Media New York 2015
Mark A. Babizhayev, David Wan-Cheng Li, Anne Kasus-Jacobi, Lepša Žorić and Jorge L. Alió (eds.)Studies on the Cornea and LensOxidative Stress in Applied Basic Research and Clinical Practice10.1007/978-1-4939-1935-2_99. Basic Review of the Oxidative Stress Role in Age-Related Cataractogenesis
(1)
Ophthalmology Department, University of Pristina, Kosovska Mitrovica, Serbia
(2)
Institute of Biochemistry, University of Pristina, Kosovska Mitrovica, Serbia
Keywords
Oxidative stressCataractRisk factorsUltraviolet raysPhysiological adaptationAntioxidants9.1 Introduction
Age-related cataract is the most common curable cause of blindness in the world. At the same time, it is the most common disease in the clinical ophthalmologic practice. Methods of treatment of cataracts through its extraction and installation of artificial lenses, although highly efficient, are a burden on the budget of each country [1, 2].
Like the aging process in the body, for decades, long accumulated oxidative damage to the lens is considered a key factor in senile cataract. In that process responsible is a balance of oxidative stress and antioxidant protection at the system level and at the local, in the eye. Mortality due to different causes is elevated in the population of elderly people with cataracts, compared to people of the same age group without cataracts, or with other eye diseases [3].
9.2 Lens of the Eye
Lens is a part of the dioptric apparatus of the eye. Thanks to the transparency and elasticity, it allows penetration of light rays to the retina and their focus in the macula. Transparency of the lens results from the optical homogeneity of its elements and depends on their structure, layout, composition, and biochemical processes in them.
In addition to refractive power, the lens has an important protective role. Through the absorption of ultraviolet part of the spectrum it protects the retina from the harmful effects of this part of the solar radiation. In this way, lens suffers photodynamic damage.
Since it is avascular, its metabolism is dependent on the composition of the aqueous humor, which surrounds it. From aqueous humor the lens receives a necessary amino acid for synthetic processes, antioxidants, and necessary hormones and glucose as an energy source. At the same time, the composition of the aqueous humor reflects the character and intensity of the biochemical processes in the lens. A high lactate level in aqueous humor was primarily a result of the anaerobic metabolism of glucose in the lens. Hydrogen peroxide in aqueous humor may be the cause, but also the consequence of oxidative processes in the lens [4, 5].
The lens is epithelial organ. However, during the life, all its cells, even those incurred during intrauterine development, remain within lens capsule, after transforming into lens fibers. Part of the energy produced in the lens is spent on their maintenance and a part on the slow mitotic cycle, which enables a very slow but steady growth of lens throughout life.
9.3 Oxidative and Photooxidative Stress
Oxygen is the condition of life of aerobic organisms, but the production of free oxygen radicals is its inevitable consequence. Hence, oxygen has a dual nature—it is necessary for life, but it is also toxic. Even normal atmospheric oxygen concentrations have slowly manifesting adverse effects.
Under normal conditions, the balance between the oxidative process and antioxidative capacity maintains stability of the composition and function of living cells. If this balance is disturbed due to increased production of radicals, reduced is the capacity of antioxidant defense system, or both processes at the same time, occurs the state of oxidative stress.
Oxidative stress has been performed physiologically in all of the breathing cells. Free radicals are created during normal cell homeostatic and defense mechanisms. Radicals which are formed during pathological processes are responsible for the damage at almost all biomolecules and manifestations are visible in the form of a number of diseases [6, 7].
The Sun, like oxygen, is a requirement for life on the Earth. Man is a “daily” organism and in his everyday activities follows a diurnal rhythm. Sunlight is necessary for a complete physical and mental development of human. Without sunlight, the development of visual function is not possible.
The human eye is exposed to ambient radiation for decades and a full spectrum of solar light has a wavelength with significant damaging potential. Photooxidative stress strats with the light absorbing organic molecules. Absorption of electromagnetic radiation of any tissue depends on its molecule excitability. Low-energy photons interact with electrons in the organic molecules and they produce a higher energy level in the outer orbitals. Thus the resulting excited state allows the formation of reactive oxygen radicals [5].
It is difficult to determine the ocular dose of ultraviolet light photodynamic damage to the human lens. In fact, it is the cumulative dose effect over a long period, which depends on solar radiation, its reflection from the stone, sand, snow, ozone depletion in the atmosphere, latitude and altitude, occupation [8], and the absorption spectrum of primary lens and its changes over a lifetime, antioxidant capacity of lenses and other endogenous factors in the eye, and the whole organism [9, 10]. It is known that artificial sources of ultraviolet rays also carry some risk of damaging the lens [8, 11].
Along with adaptation to aerobic conditions, during evolution have evolved protective, antioxidant mechanisms against the toxicity caused by free radicals. Antioxidant elements make a vast array of diverse biochemical molecules of endogenous or exogenous origin, which are activated depending on the actual mechanism of oxidative damage, their availability, and properties of the medium [5].
9.4 Cataractogenesis
Age-related cataract is a progressive opacification of the lens in people older than 45 years occurred without any known cause such as trauma, inflammation, hypocalcemia, medications or congenital factors. Cataract affects the quantity and quality of vision in various ways, depending on its type, maturity, or pigmentation.
Mitotic-capable epithelial cells are located on the anterior lens capsule and they, through the pupillary aperture, are the first lens cells facing to the electromagnetic radiation. Absorbing chromophores in the lens may initially be DNA bases and tryptophan. On this occasion arise photoproducts of DNA and subsequent changes in the type and amounts of mRNAs. Cells possess reparative enzymes of resulting damages. Incomplete repair, however, leads to permanent damage of DNA, synthesis of aberrant proteins, mutations and cell death [4, 12, 13]. Such changes are actually registered in human cataract and cataract in animal models caused by ultraviolet radiation [14, 15].
Tryptophan residues in the alpha and beta crystalline lens are easily oxidized in a hydrophilic environment. In a hydrophobic environment they are exposed to hydrogen peroxide and superoxide anion. In proteins and between them, disulfide bonds are formed, as well as with glutathione and cysteine. In this way, aggregations of proteins with altered tertiary structure are formed [14, 16]. In patients with diabetes, people with myopia and other eye diseases that process is more intense [14, 16, 17].
A moderate degree of oxidation makes proteins vulnerable to proteolysis, whereas more extensive and more intense oxidative stress consequences is a formation of aggregates of, which includes a reduction in protease activity also [18, 19]. Such a non-enzymatic oxidation is directly proportional to the concentration of hydrogen peroxide and the oxidized glutathione and reduced glutathione amount inversely.
Human lens and other lens of day organisms contain two groups of chromophores. The first is a product of tryptophan of low molecular weight having an absorption spectrum between 300 and 400 ηm and its presence is detected in the lens even before birth. Another group of pigments is related to lens proteins, appears in the second decade of life and its concentration increases with age, and the absorption spectrum extends to 500 ηm [20, 21]. Lens chromophores have a protective role basically, but those that appear in the cataractogenesis can further promote the oxidative process [22, 23].
Damage of the lipid cell membrane violates one of the conditions of cell integrity. Lipid peroxidation, according to the respective authors, is considered even as an essential causal factor of cataract [24, 25]. At the same time, the structure of membrane proteins gets disturbed [1, 25]. This leads to disruption of barrier function of the cell membrane, and membranes of cell organelles. Subjected to the oxidative modification are, as well, the calcium-adenosine triphosphatase (Ca2 +-ATPase), and sodium–potassium adenosine triphosphatase (Na +-K +-ATPase) which lead to a change in the level of intracellular calcium.
Formation and accumulation of the aforementioned colored and fluorescent oxidation products of protein intensify further photodynamic damage. Formation of protein aggregates of high molecular weight, which increases the scattering of light, is considered as the substance of the occurrence of nuclear cataracts [4, 5].
Changes in the tertiary structure of proteins, reducing the activity of antioxidant enzymes, loss of function of ion pumps and ion imbalance that, together, lead to changes in water content within the lens and the refractive index of the lens, happen in a formation of cortical cataracts [25].
9.5 The Lens Protection from Oxidation
Peptide glutathione is synthesized in the epithelium and in the cortex of the lenses in high concentrations. During the effect of light wavelength of 302 nm, it is a good cleaner (scavenger) of reactive radicals, while at higher wavelengths glutathione is a donor for glutathione peroxidase [19].
He maintains ascorbate and sulfhydryl groups of crystallines in a reduced state, and to some extent provides work of Na +-K +-ATP pump [26]. Adding glutathione to the medium in which the cells are cultured, and cataract showed a positive effect in maintaining their opacity [27, 28].
The lens crystallines, although the primary structural proteins of the lens, have a high antioxidant potential. It is primarily derived from its free sulfhydryl groups, but amino acids of a different composition can be targeted to oxidative stress [29].