PathwayType: signaling

Organ: eye

Notes: Headnote: Age-related cataract (ARC) is the leading cause of blindness in older individuals. The pathology develops due to the gradual accumulation of molecular modifications in crystallins, the major proteins in the lens, which changes crystallin structure and function and leads to clouding of the lens. To date, the widely accepted theory for the origin of ARC is related to the excessive production of reactive oxygen species (ROS). ROS are formed as a result of external and internal exposure. The external factors include UV, radiation, and smoking, while the internal factors include a decrease in intracellular antioxidant defenses which involve glutathione, SOD1, and ascorbate. Signaling description: The main molecular mechanism of the pathology is the disruption of ion transport leading to the elevation of intracellular calcium (Ca2+) and sodium (Na+). This leads to H2O efflux caused by ROS-induced membrane lipid peroxidation and direct impairment of structural proteins, crystallins, by ROS. Several mechanisms are responsible for the accumulation of ROS, which include oxygen (O2), hydrogen peroxide (H2O2), and hydroxyl radical. Elevated levels of Fe3+ and Cu2+ observed in older individuals, interact with ascorbate resulting in dehydroascorbate, H2O2, Fe2+, and Cu+ formation. Subsequently, H2O2, Fe2+, and Cu+ produce hydroxyl radicals. In addition, smoking, which is another risk factor for cataracts, also participates in ROS formation. Cd2+, present in tobacco smoke, enters the lens cells and replaces Zn2+ in the active center of SOD1 protein. As a result, SOD1 fails to detoxify O2. Further, growing evidence points to a decreased concentration of glutathione, a molecule involved in ROS detoxification, in most types of cataracts. Outcome effects: There are numerous consequences of ROS accumulation. H2O2 inhibits ATP1A1, a Na+/K ATPase, which prevents Na+ efflux. The increase in intracellular Na+ causes H2O influx, thereby provoking the separation of molecules and light scattering. ROS attack membrane lipids promoting peroxidation, which leads to the disruption of Ca2+ channels and Ca+ overload resulting in direct as well as calpain-mediated protein damage. ROS also attack and damage crystallins. In addition, oxygen radicals induce the degradation of intrinsic lens L-tryptophan to N-formylkynurenine, which increases yellow to brown coloration of the lens nucleus. Yellow-brown pigment together with the disruption of the normal architecture of the lens fibers cause the reduced transmission of light which in turn leads to visual problems. Highlighted proteins: Entities with increased level of activity are highlighted in red, and entities with decreased level of activity are highlighted in blue.

Link: https://mammal-profservices.pathwaystudio.com/app/sd?urn=urn:agi-pathway:uuid-7ac4bccd-c5ed-4f19-aea5-eaa8d8fa1eb4

CellType: epithelial cell

Organ_System: sensory system

Description: Age-related cataract (ARC) is the leading cause of blindness in older individuals. Crystallins are the main cause of the disease. Pathway is built manually using published studies.

PMID: 23222480

PMID: 10657747

PMID: 16765571

NodeType: Pathway

Pathway_Author: S. Sozin www.researchgate.net/profile/Sergey-Sozin

Source: Diseases

urn:agi-pathway:uuid-7ac4bccd-c5ed-4f19-aea5-eaa8d8fa1eb4

PS:PathwayType

PS:Description

PS:Pathway_Author

PS:Link

PS:CellType

PS:Organ_System

PS:PMID

PS:NodeType

PS:Notes

PS:Organ

PS:Source

PathwayType: signaling

Organ: eye

Notes: Headnote: Age-related cataract (ARC) is the leading cause of blindness in older individuals. The pathology develops due to the gradual accumulation of molecular modifications in crystallins, the major proteins in the lens, which changes crystallin structure and function and leads to clouding of the lens. To date, the widely accepted theory for the origin of ARC is related to the excessive production of reactive oxygen species (ROS). ROS are formed as a result of external and internal exposure. The external factors include UV, radiation, and smoking, while the internal factors include a decrease in intracellular antioxidant defenses which involve glutathione, SOD1, and ascorbate. Signaling description: The main molecular mechanism of the pathology is the disruption of ion transport leading to the elevation of intracellular calcium (Ca2+) and sodium (Na+). This leads to H2O efflux caused by ROS-induced membrane lipid peroxidation and direct impairment of structural proteins, crystallins, by ROS. Several mechanisms are responsible for the accumulation of ROS, which include oxygen (O2), hydrogen peroxide (H2O2), and hydroxyl radical. Elevated levels of Fe3+ and Cu2+ observed in older individuals, interact with ascorbate resulting in dehydroascorbate, H2O2, Fe2+, and Cu+ formation. Subsequently, H2O2, Fe2+, and Cu+ produce hydroxyl radicals. In addition, smoking, which is another risk factor for cataracts, also participates in ROS formation. Cd2+, present in tobacco smoke, enters the lens cells and replaces Zn2+ in the active center of SOD1 protein. As a result, SOD1 fails to detoxify O2. Further, growing evidence points to a decreased concentration of glutathione, a molecule involved in ROS detoxification, in most types of cataracts. Outcome effects: There are numerous consequences of ROS accumulation. H2O2 inhibits ATP1A1, a Na+/K ATPase, which prevents Na+ efflux. The increase in intracellular Na+ causes H2O influx, thereby provoking the separation of molecules and light scattering. ROS attack membrane lipids promoting peroxidation, which leads to the disruption of Ca2+ channels and Ca+ overload resulting in direct as well as calpain-mediated protein damage. ROS also attack and damage crystallins. In addition, oxygen radicals induce the degradation of intrinsic lens L-tryptophan to N-formylkynurenine, which increases yellow to brown coloration of the lens nucleus. Yellow-brown pigment together with the disruption of the normal architecture of the lens fibers cause the reduced transmission of light which in turn leads to visual problems. Highlighted proteins: Entities with increased level of activity are highlighted in red, and entities with decreased level of activity are highlighted in blue.

Link: https://mammal-profservices.pathwaystudio.com/app/sd?urn=urn:agi-pathway:uuid-7ac4bccd-c5ed-4f19-aea5-eaa8d8fa1eb4

CellType: epithelial cell

Organ_System: sensory system

Description: Age-related cataract (ARC) is the leading cause of blindness in older individuals. Crystallins are the main cause of the disease. Pathway is built manually using published studies.

PMID: 23222480

PMID: 10657747

PMID: 16765571

NodeType: Pathway

Pathway_Author: S. Sozin www.researchgate.net/profile/Sergey-Sozin

Source: Diseases

urn:agi-pathway:uuid-7ac4bccd-c5ed-4f19-aea5-eaa8d8fa1eb4

Age-Related Cataract

uuid-7ac4bccd-c5ed-4f19-aea5-eaa8d8fa1eb4

Age-Related Cataract

urn:agi-folder:a

urn:agi-folder:plasma_membrane

urn:agi-folder:cataract

urn:agi-folder:sensory_system

urn:agi-folder:a

urn:agi-folder:plasma_membrane

urn:agi-folder:cataract

urn:agi-folder:sensory_system