metabolic stress

Cells — Journal Article

matched text: “metabolic stress”

PROM1-associated retinal degeneration encompasses dominant macular disease and recessive, often more widespread photoreceptor degeneration. A common gene name does not make these conditions mechanistically or therapeutically interchangeable. This scoping review and evidence map integrates clinical genetics, natural history, membrane biology, photoreceptor and retinal pigment epithelium (RPE) models, preclinical interventions and dated human-study records. The strongest translational advance is rescue in PROM1-deficient experimental systems, demonstrated in patient-derived organoids and in knockout mice. Post-onset benefit is reported in a full-text mouse study and in a separate conference abstract. The principal unresolved transfer is to dominant mutant disease, where augmentation, mutant suppression and combined treatment require direct comparison. The mechanistic literature extends beyond outer-segment morphogenesis: direct RPE experiments implicate autophagic flux and outer-segment clearance, while light-sensitive knockout models implicate endothelin, insulin-like growth factor 1 (IGF1) and metabolic stress. These pathways require compartment-specific interpretation. Human quantitative autofluorescence findings constrain a universal bisretinoid-excess explanation, and protective local endothelin effects in other retinal genotypes argue against treating the pathway as uniformly harmful. Clinical endpoints are correspondingly stratified: dominant atrophy expansion, recessive ellipsoid-zone contraction and layer-specific thinning on optical coherence tomography (OCT) measure different processes and have different floor effects. Human studies with explicit or broader genetic eligibility may admit PROM1 disease, but for most of them the records show who could enter rather than who did, or what followed. Seven experimental programmes connect these distinctions to testable comparisons, each set out as the decisive contrast, the safeguard it needs, and the decision it would settle. The resulting framework distinguishes candidate therapies by allele, compartment and disease stage.

matched text: “metabolic stress”