This is a mechanism module, not a specific disease. Disorder entries reference individual nodes via conforms_to (e.g., "photoreceptor_degeneration#Rod Photoreceptor Apoptosis"). The module defines the expected pathophysiology structure; conforming nodes in disorder files should include the corresponding cell types, biological processes, and causal edges, specialized to the gene class involved. Key gene-class substitutions conforming nodes should make at the trigger node: phototransduction defects (e.g., RHO, PDE6B, CNGB1), photoreceptor ciliary/structural defects (e.g., RPGR, RP1, peripherin/PRPH2), RPE visual-cycle defects (e.g., RPE65, ABCA4), and pre-mRNA splicing-factor defects (e.g., PRPF31).
Photoreceptor Gene Defect
trigger
The initiating lesion is a mutation in a gene required for photoreceptor function or homeostasis. Across retinitis pigmentosa subtypes the gene class varies - phototransduction-cascade components, outer-segment and connecting-cilium structural proteins, RPE visual-cycle enzymes, or pre-mRNA splicing factors - but the mutation is expressed in or critically impairs rod photoreceptors. The defect disrupts phototransduction, outer-segment renewal, or retinol metabolism, destabilizing the photoreceptor before overt cell death.
Downstream
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Photoreceptor Metabolic and Oxidative Stress
Show evidence (2 references)
"Alterations in the activity of the phototransduction cascade, such as changes affecting the renewal and shedding of the photoreceptor OSs, visual transduction, and/or retinol metabolism have a great impact on the health of the retina. Mutations within any of the molecules responsible for these..."
Establishes that mutations across diverse photoreceptor gene classes (phototransduction, outer-segment renewal, retinol/visual-cycle metabolism) are the conserved initiating lesion of inherited retinal degeneration. Evidence source is OTHER because this is a review chapter synthesizing multiple study types.
"The various mechanisms underlying rod degeneration primarily rely on genetic mutations, leading to night blindness initially."
Confirms that the rod-expressed genetic mutation is the primary driver of the cascade. Evidence source is OTHER because this is a review.
Rod Photoreceptor Apoptosis
central effector
Accumulated metabolic and oxidative stress, dysregulated second messengers, and unfolded-protein-response signaling converge on programmed death of rod photoreceptors. Apoptosis is the central, conserved effector mechanism of rod loss across retinitis pigmentosa subtypes, although calpain-mediated and other non-apoptotic death pathways can also contribute. Because the disease mutation is expressed in rods, this is the primary, cell-autonomous death step.
Downstream
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Secondary Cone Degeneration and Outer Retinal Thinning
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"In RP, the progressive atrophy of the rod photoreceptor cells leads to the secondary death of the cones."
Establishes progressive rod photoreceptor death as the primary, cell-autonomous lesion that precedes secondary cone loss. Evidence source is OTHER because this is a review chapter.
"This photoreceptor cell death has been thought to result from a caspase-dependent apoptotic mechanism"
Supports apoptosis (caspase-dependent) as the conserved effector mechanism of photoreceptor death. Evidence source is OTHER because this is a review.
Secondary Cone Degeneration and Outer Retinal Thinning
effector
After rods are largely eliminated, cone photoreceptors degenerate in a characteristic non-cell-autonomous pattern even though the disease mutation is usually not expressed in cones. Proposed drivers include loss of rod-derived trophic support, nutrient and metabolic shortage, oxidative damage from the high post-rod-loss oxygen environment, and microglial inflammation. Progressive photoreceptor loss thins the outer retina. Cone death is the step that converts night blindness into disabling loss of daytime and central vision.
Downstream
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Progressive Visual Field Loss and Blindness
Show evidence (2 references)
"After rods die, cone photoreceptors slowly degenerate in a characteristic pattern."
Directly states the conserved sequence of secondary cone degeneration following rod death. Evidence source is OTHER because this is a review.
"In all forms of RP, the genetic mutation is expressed exclusively in rods; however, cones die too. The secondary death of cones in RP remains somewhat mysterious."
Establishes the non-cell-autonomous nature of cone death - cones lack the causal mutation yet still degenerate. Evidence source is OTHER because this is a review.
Progressive Visual Field Loss and Blindness
consequence
The clinical phenotype of retinitis pigmentosa / rod-cone dystrophy. Rod loss first produces night blindness (nyctalopia), then constriction of the peripheral visual field (tunnel vision), with central vision relatively preserved until cone degeneration advances. Eventually central vision is lost, progressing toward legal blindness. This is the conserved terminal consequence shared across all genetic subtypes.
Show evidence (2 references)
"Affected individuals often present with night blindness (nyctalopia) and constricted visual fields (tunnel vision), but central vision (e.g. reading vision, facial recognition) is normal or nearly normal. Eventually central vision is lost as the cone cells degenerate."
Directly describes the conserved clinical progression - night blindness, then peripheral field constriction, then central vision loss - that defines the consequence node. Evidence source is OTHER because this is a review chapter.
"Rod cell death causes night blindness, but visual disability and blindness result from cone degeneration"
Confirms that night blindness arises from rod loss while disabling blindness results from secondary cone degeneration, tying the terminal phenotype to the upstream cell-death chain. Evidence source is OTHER because this is a review.