Pathophysiology Nodes

5
5 shared nodes are defined in this module.

Cell Types

3
rod photoreceptor cell CL:0000604 Cell Ontology (CL) Relation: this mechanism module involves this cell type This mechanism module involves rod photoreceptor cell (CL:0000604). CL:0000604 is a cell type from the Cell Ontology. photoreceptor cell CL:0000210 Cell Ontology (CL) Relation: this mechanism module involves this cell type This mechanism module involves photoreceptor cell (CL:0000210). CL:0000210 is a cell type from the Cell Ontology. cone photoreceptor cell CL:0000573 Cell Ontology (CL) Relation: this mechanism module involves this cell type This mechanism module involves cone photoreceptor cell (CL:0000573). CL:0000573 is a cell type from the Cell Ontology.

Biological Processes

6
Phototransduction GO:0007602 Gene Ontology (GO) Relation: this mechanism module involves this biological process This mechanism module involves abnormal Phototransduction (GO:0007602). GO:0007602 is a biological process from the Gene Ontology. ABNORMAL Photoreceptor cell maintenance GO:0045494 Gene Ontology (GO) Relation: this mechanism module involves this biological process This mechanism module involves decreased Photoreceptor cell maintenance (GO:0045494). GO:0045494 is a biological process from the Gene Ontology. DECREASED Response to oxidative stress GO:0006979 Gene Ontology (GO) Relation: this mechanism module involves this biological process This mechanism module involves increased Response to oxidative stress (GO:0006979). GO:0006979 is a biological process from the Gene Ontology. INCREASED Endoplasmic reticulum unfolded protein response GO:0030968 Gene Ontology (GO) Relation: this mechanism module involves this biological process This mechanism module involves increased Endoplasmic reticulum unfolded protein response (GO:0030968). GO:0030968 is a biological process from the Gene Ontology. INCREASED Neuron apoptotic process GO:0051402 Gene Ontology (GO) Relation: this mechanism module involves this biological process This mechanism module involves increased Neuron apoptotic process (GO:0051402). GO:0051402 is a biological process from the Gene Ontology. INCREASED Visual perception GO:0007601 Gene Ontology (GO) Relation: this mechanism module involves this biological process This mechanism module involves decreased Visual perception (GO:0007601). GO:0007601 is a biological process from the Gene Ontology. DECREASED
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Notes

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).

Used By Disorder Entries

25

Pathograph

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Pathograph: causal mechanism network for Inherited Photoreceptor Degeneration Module Interactive directed graph showing how this shared module's pathophysiology nodes connect.

Pathophysiology

5
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.
rod photoreceptor cell CL:0000604 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves rod photoreceptor cell, annotated with retinal rod cell (CL:0000604). CL:0000604 is a cell type from the Cell Ontology. photoreceptor cell CL:0000210 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves photoreceptor cell (CL:0000210). CL:0000210 is a cell type from the Cell Ontology.
Phototransduction GO:0007602 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal Phototransduction (GO:0007602). GO:0007602 is a biological process from the Gene Ontology. ABNORMAL Photoreceptor cell maintenance GO:0045494 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased Photoreceptor cell maintenance (GO:0045494). GO:0045494 is a biological process from the Gene Ontology. DECREASED
Photoreceptor Metabolic and Oxidative Stress
amplifier
The gene defect imposes metabolic and oxidative stress on the photoreceptor. Disrupted phototransduction and dysregulated cGMP/Ca2+ handling, together with retention of un- or mis-folded proteins in the endoplasmic reticulum, activate the unfolded protein response. As rods are lost, falling oxygen consumption raises outer-retinal oxygen tension, driving superoxide and reactive-species production that overwhelms antioxidant defenses. This amplification step bridges the primary lesion to photoreceptor cell death.
photoreceptor cell CL:0000210 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves photoreceptor cell (CL:0000210). CL:0000210 is a cell type from the Cell Ontology.
Response to oxidative stress GO:0006979 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased Response to oxidative stress (GO:0006979). GO:0006979 is a biological process from the Gene Ontology. INCREASED Endoplasmic reticulum unfolded protein response GO:0030968 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased Endoplasmic reticulum unfolded protein response (GO:0030968). GO:0030968 is a biological process from the Gene Ontology. INCREASED
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.
rod photoreceptor cell CL:0000604 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves rod photoreceptor cell, annotated with retinal rod cell (CL:0000604). CL:0000604 is a cell type from the Cell Ontology.
Neuron apoptotic process GO:0051402 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased Neuron apoptotic process (GO:0051402). GO:0051402 is a biological process from the Gene Ontology. INCREASED
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.
cone photoreceptor cell CL:0000573 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves cone photoreceptor cell, annotated with retinal cone cell (CL:0000573). CL:0000573 is a cell type from the Cell Ontology.
Neuron apoptotic process GO:0051402 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased Neuron apoptotic process (GO:0051402). GO:0051402 is a biological process from the Gene Ontology. INCREASED Response to oxidative stress GO:0006979 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased Response to oxidative stress (GO:0006979). GO:0006979 is a biological process from the Gene Ontology. INCREASED
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.
Visual perception GO:0007601 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased Visual perception (GO:0007601). GO:0007601 is a biological process from the Gene Ontology. DECREASED