Retinal Phd2 ablation partially rescues Crb1Crb2-associated Leber congenital amaurosis and alters metabolic signaling

Retinal Phd2 deletion in conditional Crb1/Crb2-deficient mice partially improves scotopic responses and significantly raises optomotor spatial-frequency thresholds, without restoring b-wave or cone-mediated function.

• Why it matters: CRB1-associated LCA lacks restorative treatments, and the study tests whether mutation-independent neuroprotection can be achieved by targeting retinal metabolic signaling.
• What they did: In conditional Crb1/Crb2-deficient mice, Phd2 was additionally deleted throughout the neural retina, and retinal function, structure, behavior, and glycolysis-related gene/protein expression were assessed at one and two months.
• The result: Phd2Crb1Crb2 retinas show more organized photoreceptor rosettes and improved polarity/synapse protein compartmentalization, with temporally selective metabolic shifts (Glut1/Vegfa transcripts at 1M; GLUT1/LDHA proteins at 2M), supporting PHD2-associated metabolic signaling as a disease-modifying target.