This is a mechanism module, not a specific disease. Disorder entries reference individual nodes via conforms_to (e.g., "glaucoma_optic_neuropathy#Retinal Ganglion Cell Apoptosis"). Conforming nodes should substitute the disorder-specific cause of raised outflow resistance (juxtacanalicular ECM accumulation in POAG, pupillary block/angle closure in angle-closure glaucoma, fibrillar exfoliation material in exfoliation glaucoma, MYOC/trabecular gene defects in juvenile glaucoma). Normal-tension glaucoma is a partial exception in which RGC loss occurs at statistically normal IOP.
Trabecular Meshwork Outflow Dysfunction
trigger
The trabecular meshwork in the iridocorneal angle is the principal drainage pathway for aqueous humor. Accumulation and reorganization of extracellular matrix in the juxtacanalicular tissue, loss of trabecular cellularity, and cytoskeletal stiffening increase resistance to aqueous outflow. This outflow dysfunction is the conserved initiating lesion across most glaucomas.
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Elevated Intraocular Pressure
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"The trabecular meshwork, located within the iridocorneal angle, is the main pathway for drainage of aqueous humor (AH) out of the eye, and its dysfunction is responsible for the IOP elevation."
Directly establishes trabecular meshwork dysfunction as the cause of impaired aqueous outflow and IOP elevation, the conserved initiating lesion. Evidence source is OTHER because this is a literature review.
Elevated Intraocular Pressure
amplifier
Increased resistance to aqueous humor drainage raises intraocular pressure. Elevated IOP is the principal modifiable risk factor for glaucoma and the proximate mechanical stressor transmitted to the optic nerve head and lamina cribrosa, where the retinal ganglion cell axons exit the eye.
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Retinal Ganglion Cell Apoptosis
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"Glaucoma is a blinding optic neuropathy, the main risk factor for which is increased intraocular pressure (IOP)."
Identifies elevated IOP as the principal risk factor linking outflow dysfunction to glaucomatous optic neuropathy. Evidence source is OTHER because this is a literature review.
"The resistance of AH drainage through this pathway results in IOP increase and TM degeneration"
Confirms that aqueous outflow resistance directly produces the IOP increase this node represents. Evidence source is OTHER because this is a review article.
Retinal Ganglion Cell Apoptosis
central effector
Pressure-related mechanical stress at the optic nerve head, combined with oxidative stress, impaired axonal transport, and neurotrophin deprivation, triggers apoptosis of retinal ganglion cells. This is the central effector step of glaucomatous neurodegeneration and is shared across glaucoma subtypes.
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Optic Nerve Degeneration and Neuroinflammation
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"This disease is a neurodegenerative disorder characterized by high intraocular pressure, loss of retinal ganglion cells (apoptosis)."
Directly characterizes glaucoma as a neurodegenerative disorder defined by apoptotic loss of retinal ganglion cells, the central effector of this module. Evidence source is OTHER because this is a review article.
"they produce apoptosis of the neurons in the optic nerve head, degradation of the trabecular meshwork cells."
Links oxidative free-radical injury to apoptosis of optic-nerve-head neurons and trabecular degeneration, supporting the apoptotic mechanism. Evidence source is OTHER because this is a review article.
Optic Nerve Degeneration and Neuroinflammation
effector
Progressive retinal ganglion cell loss is accompanied by optic nerve axon degeneration and a glial neuroinflammatory response that further accelerates neurodegeneration. Oxidative DNA damage accumulating in the degenerating tissue amplifies this neuroinflammatory drive.
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Progressive Glaucomatous Optic Neuropathy
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"oxidative DNA damage accumulates in this degenerating TM, accelerating a neuroinflammation process which drives the neurodegeneration in POAG pathology"
Describes a neuroinflammatory process accelerating the neurodegeneration that characterizes this effector step. Evidence source is OTHER because this is a review article.
Progressive Glaucomatous Optic Neuropathy
consequence
Cumulative retinal ganglion cell and axon loss produces the characteristic optic disc cupping, retinal nerve fiber layer thinning, and progressive, irreversible visual field loss that define glaucoma as a clinical entity.
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"progressive degeneration of retinal ganglion cells (RGC) with a specific pattern of changes in the optic nerve head and retinal nerve fiber layer"
Describes the progressive RGC degeneration with optic nerve head and nerve fiber layer changes that define glaucomatous optic neuropathy, the endpoint of this module. Evidence source is OTHER because this is a review article.
"Glaucoma is a blinding optic neuropathy"
Confirms that the clinical consequence of this pathway is a blinding optic neuropathy. Evidence source is OTHER because this is a literature review.