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Glaucoma is a group of eye conditions characterized by progressive optic nerve damage caused by an increase in intraocular pressure (IOP). Glaucoma is the 2nd most common cause of blindness worldwide and the 2nd most common cause of blindness in the US. About 3 million Americans and 64 million people worldwide have glaucoma, but only half are aware of it. Glaucoma can occur at any age but is 6 times more common among people over the age of 60.
Glaucoma is the result of damage to the optic nerve caused by increased pressure in the eye. As this nerve gradually deteriorates, blind spots develop in the visual field. Elevated eye pressure is due to a buildup of a fluid (aqueous humor) that is produced by ciliary bodies and flows throughout the inside of the eye. This internal fluid normally drains out through a tissue called the trabecular meshwork. The trabecular meshwork is the spongy tissue located at the angle where the iris and cornea meet and it is responsible for regulating the outflow of aqueous humor. Through trabecular meshwork, 80-90 percent of aqueous humor flows out of the eye into the Schlemm’s Canal which a ring-like passageway around the outer angle of the anterior chamber in front of the iris. From the canal, the liquid enters the veins. When fluid is overproduced or the drainage system doesn't work properly, the fluid can't flow out at its normal rate and eye pressure increases.
The trabecular meshwork is the eye’s lymphatic drainage system. It consists of two parts: a non-filtering portion and a filtering portion. The non-filtering portion consists mainly of the trabecular cells which are highly phagocytic cells that remove particles, cellular debris, and proteins from the aqueous humor. The filtering portion is a network of beams covered with endothelial cells. The trabecular meshwork is a contractile tissue with properties similar to smooth muscle. The contraction of the endothelial cells reduces the size of the intercellular spaces and decreases permeability. When the endothelial cells relax, the permeability increases.1 Disruption of the contractibility of the trabecular meshwork in an aged eye with increased contraction can lead to glaucoma development.
A cataract is a clouding of the normally clear lens of the eye. The eye lens is positioned behind the iris and focuses light that passes into the eye, producing a clear, sharp image on the retina. The retina is the light-sensitive membrane that functions like the film in a camera. For people who have cataracts, seeing through cloudy lenses is a bit like looking through a frosty or fogged-up window. Clouded vision caused by cataracts can make it more difficult to read and drive a car, especially at night. Most cataracts develop slowly and don’t disturb eyesight early on. But with time, cataracts will eventually interfere with an individual’s vision.
Cataract is the leading cause of reversible vision loss in the world. There are several risk factors for cataract formation with age being the most impactful. Age-related cataracts are responsible for nearly half of all blindness worldwide and half of all visual impairment in the United States. Other factors such as diabetes, glaucoma, and heritability are also known to be significant risks for cataract development. In addition, ultraviolet B radiation (UV-B), body mass index (BMI), smoking, diet, exposure to hyperbaric oxygen, and corticosteroids have been identified as extrinsic or environmental risk factors for cataract.
Oxidative stress is a significant factor in the pathogenesis of senile cataract. The oxidative processes increase with age in the human lens that leads to an aggregation of the crystallin inside the fiber cell causing opaque lenses. A crystallin is a water-soluble structural protein in the lens and the cornea and it accounts for the transparency of the structure. The main function of crystallin in the lens is to increase the refractive index while not obstructing light. Crystallin from a vertebrate eye lens are classified into three main types: alpha, beta and gamma crystallin. Transparency in the eye lens is maintained via specific, functional interactions among the structural βγ- and chaperone α-crystallin’s. Crosslink of these proteins cause diminished transparency.2
Age-related nuclear cataract is initiated in the central core of the lens, which contains primary fiber cells. Oxidative stress is a key factor in nuclear cataract formation. An increase of reactive oxygen species such as through UV exposure or increased oxygen partial pressure and reduction of endogenous antioxidants such as glutathione (GSH) or decrease in antioxidant enzymes change the redox state. It causes lens crystallin proteins to change sulfhydryl groups to thiolated or become cross-linked. The resultant high molecular weight aggregates become insoluble which affects lens transparency, increases yellowing of the lens nucleus, and eventually cause nuclear cataract formation.
The nutrient delivery and waste removal are actively operated via an extracellular route driven by the lens microcirculation system. Such microcirculation system employs a circulating current of Na+ ions that enters at the poles and travels into the lens via the extracellular clefts between fiber cells and returns towards the surface at the equator by crossing fiber cell membranes, where it is actively removed by Na+ pumps at the lens equator using ATP as the energy source.3 This circulating ionic current creates a fluid flow that powers a nutrient/antioxidant uptake and removal of metabolic waste from the center core. The peripheral differentiating fiber cells contain mitochondria, while mature fiber cells are devoid of mitochondria. Reduced ATP production by the differentiating fiber cells due to aging can compromise the lens’s microcirculation system resulting in undersupply of the GSH to the lens center and leads to the development of nuclear cataract.3
An increase of glucose triggers the aldose reductase to catalyze the conversion of glucose to sorbitol, the first step of polyol pathway. This reaction is NADPH dependent and the conversion of NADP to NADPH consumes GSH.4 Depletion of GSH causes an increase in ROS. In addition, sorbitol is an osmolyte which increase osmotic stress and attracts fluid to the fiber cell causing fiber cell swelling and liquefaction in the lens cortex. Cell swelling can also cause depolarization with an influx of sodium and calcium ions which triggers the activation of calcium-dependent proteases that damage the cell protein structure. The high glucose level can also cause protein glycation of crystallins resulting in decreased solubility and formation of high molecular weight aggregates and cataract formation.4
The mechanisms to maintain low oxygen partial pressure are barriers to oxygen permeation across layers of fiber-cell membranes and oxygen consumption within the lens interior. The oxygen consumption mechanism is through the mitochondrial respiration in the lens epithelium. The lens epithelium, located in the anterior portion of the lens between the lens capsule and the lens fibers, is a simple cuboidal epithelium. The cells of the lens epithelium regulate most of the homeostatic functions of the lens. In most tissues, oxygen partial pressures below 3% (~22 mmHg) are considered hypoxic. The oxygen level near the anterior lens epithelium can be as low as 0.4% (~3 mmHg) due to the oxygen consumption by the mitochondrial in the epithelium.5 Mitochondria are abundant in the epithelium and differentiating fibers, but mature fibers in the core of the lens lack mitochondria. Mitochondria account for approximately 90% of the total oxygen consumption by the lens.5
Decreased nutritional supply due to the reduction of microcirculation of the eye microcapillaries from aging and other factors such as, radiation accumulation, can cause mitochondria decay in number and function which leads to low oxygen consumption in older people. Low oxygen consumption not only causes increased oxygen partial pressure at the lens but also contributes to decreased metabolism in the epithelium to support the lens structure and function leading to the cataract development. In a study involving patients treated with long-term hyperbaric oxygen therapy, it was demonstrated that the older human lens is more susceptible to oxygen-induced damage. In addition, lower oxygen consumption rate in lens equilibrium cells is also found in patients with diabetes or glaucoma which could contribute to cataract development.
The second mechanisms to maintain low oxygen partial pressure are barriers to oxygen permeation across layers of fiber-cell membranes. The lipid bilayer portion of lens membranes, with its unique lipid composition and structure, forms significant barriers to oxygen transport. As the lens need last many years any small amount of oxygen is harmful. During aging process additional mechanism have developed to ensure the lipid bilayer is even less permeable to oxygen.
The fiber-cell membrane phospholipid (PL) composite changes drastically during aging with the increase of sphingolipid content and depletion of phosphatidylcholine. The saturation levels of PL acyl chains also increase with age. The most characteristic change with age is the increase of cholesterol (chol) content up to the chol/PL molar ratio of 4. For the elderly population, the high chol content is often induced formation of cholesterol crystals. These fiber cell membrane compositions change significantly with increased lens stiffness through the increased membrane mechanical rigidity. The result of increased lens stiffness is that fiber cell plasma membranes become less permeable to oxygen, which help to maintain lens transparency and protect against oxidative damage and cataract development. Such protection against cataract development is at the cost of losing lens flexibility which compromises the focusing property of the lens. The high cholesterol content in fiber-cell plasma membranes is critical to ensure that the lipid bilayer portion of the membranes become even more hydrophobic for permeation of polar molecules. The need for high chol in the eye lens is suggested by the observations that inherited defects in chol metabolism enzymes and the use of cholesterol-biosynthesis-inhibiting drugs contribute to cataract formation. Retrospective cohort studies comparing the risk of development of cataracts between statin users and non-users showed that the risk of cataract development was increased among statin users.
Login as practitioner to view Wellness Recommendation.
Glaucoma is a group of eye conditions characterized by progressive optic nerve damage caused by an increase in intraocular pressure (IOP). Glaucoma is the 2nd most common cause of blindness worldwide and the 2nd most common cause of blindness in the US. About 3 million Americans and 64 million people worldwide have glaucoma, but only half are aware of it. Glaucoma can occur at any age but is 6 times more common among people over the age of 60.
Glaucoma is the result of damage to the optic nerve caused by increased pressure in the eye. As this nerve gradually deteriorates, blind spots develop in the visual field. Elevated eye pressure is due to a buildup of a fluid (aqueous humor) that is produced by ciliary bodies and flows throughout the inside of the eye. This internal fluid normally drains out through a tissue called the trabecular meshwork. The trabecular meshwork is the spongy tissue located at the angle where the iris and cornea meet and it is responsible for regulating the outflow of aqueous humor. Through trabecular meshwork, 80-90 percent of aqueous humor flows out of the eye into the Schlemm’s Canal which a ring-like passageway around the outer angle of the anterior chamber in front of the iris. From the canal, the liquid enters the veins. When fluid is overproduced or the drainage system doesn't work properly, the fluid can't flow out at its normal rate and eye pressure increases.
The trabecular meshwork is the eye’s lymphatic drainage system. It consists of two parts: a non-filtering portion and a filtering portion. The non-filtering portion consists mainly of the trabecular cells which are highly phagocytic cells that remove particles, cellular debris, and proteins from the aqueous humor. The filtering portion is a network of beams covered with endothelial cells. The trabecular meshwork is a contractile tissue with properties similar to smooth muscle. The contraction of the endothelial cells reduces the size of the intercellular spaces and decreases permeability. When the endothelial cells relax, the permeability increases.1 Disruption of the contractibility of the trabecular meshwork in an aged eye with increased contraction can lead to glaucoma development.
A cataract is a clouding of the normally clear lens of the eye. The eye lens is positioned behind the iris and focuses light that passes into the eye, producing a clear, sharp image on the retina. The retina is the light-sensitive membrane that functions like the film in a camera. For people who have cataracts, seeing through cloudy lenses is a bit like looking through a frosty or fogged-up window. Clouded vision caused by cataracts can make it more difficult to read and drive a car, especially at night. Most cataracts develop slowly and don’t disturb eyesight early on. But with time, cataracts will eventually interfere with an individual’s vision.
Cataract is the leading cause of reversible vision loss in the world. There are several risk factors for cataract formation with age being the most impactful. Age-related cataracts are responsible for nearly half of all blindness worldwide and half of all visual impairment in the United States. Other factors such as diabetes, glaucoma, and heritability are also known to be significant risks for cataract development. In addition, ultraviolet B radiation (UV-B), body mass index (BMI), smoking, diet, exposure to hyperbaric oxygen, and corticosteroids have been identified as extrinsic or environmental risk factors for cataract.
Oxidative stress is a significant factor in the pathogenesis of senile cataract. The oxidative processes increase with age in the human lens that leads to an aggregation of the crystallin inside the fiber cell causing opaque lenses. A crystallin is a water-soluble structural protein in the lens and the cornea and it accounts for the transparency of the structure. The main function of crystallin in the lens is to increase the refractive index while not obstructing light. Crystallin from a vertebrate eye lens are classified into three main types: alpha, beta and gamma crystallin. Transparency in the eye lens is maintained via specific, functional interactions among the structural βγ- and chaperone α-crystallin’s. Crosslink of these proteins cause diminished transparency.2
Age-related nuclear cataract is initiated in the central core of the lens, which contains primary fiber cells. Oxidative stress is a key factor in nuclear cataract formation. An increase of reactive oxygen species such as through UV exposure or increased oxygen partial pressure and reduction of endogenous antioxidants such as glutathione (GSH) or decrease in antioxidant enzymes change the redox state. It causes lens crystallin proteins to change sulfhydryl groups to thiolated or become cross-linked. The resultant high molecular weight aggregates become insoluble which affects lens transparency, increases yellowing of the lens nucleus, and eventually cause nuclear cataract formation.
The nutrient delivery and waste removal are actively operated via an extracellular route driven by the lens microcirculation system. Such microcirculation system employs a circulating current of Na+ ions that enters at the poles and travels into the lens via the extracellular clefts between fiber cells and returns towards the surface at the equator by crossing fiber cell membranes, where it is actively removed by Na+ pumps at the lens equator using ATP as the energy source.3 This circulating ionic current creates a fluid flow that powers a nutrient/antioxidant uptake and removal of metabolic waste from the center core. The peripheral differentiating fiber cells contain mitochondria, while mature fiber cells are devoid of mitochondria. Reduced ATP production by the differentiating fiber cells due to aging can compromise the lens’s microcirculation system resulting in undersupply of the GSH to the lens center and leads to the development of nuclear cataract.3
An increase of glucose triggers the aldose reductase to catalyze the conversion of glucose to sorbitol, the first step of polyol pathway. This reaction is NADPH dependent and the conversion of NADP to NADPH consumes GSH.4 Depletion of GSH causes an increase in ROS. In addition, sorbitol is an osmolyte which increase osmotic stress and attracts fluid to the fiber cell causing fiber cell swelling and liquefaction in the lens cortex. Cell swelling can also cause depolarization with an influx of sodium and calcium ions which triggers the activation of calcium-dependent proteases that damage the cell protein structure. The high glucose level can also cause protein glycation of crystallins resulting in decreased solubility and formation of high molecular weight aggregates and cataract formation.4
The mechanisms to maintain low oxygen partial pressure are barriers to oxygen permeation across layers of fiber-cell membranes and oxygen consumption within the lens interior. The oxygen consumption mechanism is through the mitochondrial respiration in the lens epithelium. The lens epithelium, located in the anterior portion of the lens between the lens capsule and the lens fibers, is a simple cuboidal epithelium. The cells of the lens epithelium regulate most of the homeostatic functions of the lens. In most tissues, oxygen partial pressures below 3% (~22 mmHg) are considered hypoxic. The oxygen level near the anterior lens epithelium can be as low as 0.4% (~3 mmHg) due to the oxygen consumption by the mitochondrial in the epithelium.5 Mitochondria are abundant in the epithelium and differentiating fibers, but mature fibers in the core of the lens lack mitochondria. Mitochondria account for approximately 90% of the total oxygen consumption by the lens.5
Decreased nutritional supply due to the reduction of microcirculation of the eye microcapillaries from aging and other factors such as, radiation accumulation, can cause mitochondria decay in number and function which leads to low oxygen consumption in older people. Low oxygen consumption not only causes increased oxygen partial pressure at the lens but also contributes to decreased metabolism in the epithelium to support the lens structure and function leading to the cataract development. In a study involving patients treated with long-term hyperbaric oxygen therapy, it was demonstrated that the older human lens is more susceptible to oxygen-induced damage. In addition, lower oxygen consumption rate in lens equilibrium cells is also found in patients with diabetes or glaucoma which could contribute to cataract development.
The second mechanisms to maintain low oxygen partial pressure are barriers to oxygen permeation across layers of fiber-cell membranes. The lipid bilayer portion of lens membranes, with its unique lipid composition and structure, forms significant barriers to oxygen transport. As the lens need last many years any small amount of oxygen is harmful. During aging process additional mechanism have developed to ensure the lipid bilayer is even less permeable to oxygen.
The fiber-cell membrane phospholipid (PL) composite changes drastically during aging with the increase of sphingolipid content and depletion of phosphatidylcholine. The saturation levels of PL acyl chains also increase with age. The most characteristic change with age is the increase of cholesterol (chol) content up to the chol/PL molar ratio of 4. For the elderly population, the high chol content is often induced formation of cholesterol crystals. These fiber cell membrane compositions change significantly with increased lens stiffness through the increased membrane mechanical rigidity. The result of increased lens stiffness is that fiber cell plasma membranes become less permeable to oxygen, which help to maintain lens transparency and protect against oxidative damage and cataract development. Such protection against cataract development is at the cost of losing lens flexibility which compromises the focusing property of the lens. The high cholesterol content in fiber-cell plasma membranes is critical to ensure that the lipid bilayer portion of the membranes become even more hydrophobic for permeation of polar molecules. The need for high chol in the eye lens is suggested by the observations that inherited defects in chol metabolism enzymes and the use of cholesterol-biosynthesis-inhibiting drugs contribute to cataract formation. Retrospective cohort studies comparing the risk of development of cataracts between statin users and non-users showed that the risk of cataract development was increased among statin users.
Login as practitioner to view Wellness Recommendation.