biostudies-literatureCaruso SMNEI NIH HHSNational Eye InstituteFoundation Fighting Blindnesse185796https://www.ebi.ac.uk/biostudies/studies/S-EPMC11957697biostudies-literatureUnknown135(7)Neuroretinal degenerations including retinitis pigmentosa (RP) comprise a heterogeneous collection of pathogenic mutations that ultimately result in blindness. Despite recent advances in precision medicine, therapies for rarer mutations are hindered by burdensome developmental costs. To this end, Von Hippel-Lindau (VHL) is an attractive therapeutic target to treat RP. By ablating VHL in rod photoreceptors and elevating hypoxia-inducible factor (HIF) levels, we demonstrate a path to therapeutically enhancing glycolysis independent of the underlying genetic variant that slows degeneration of both rod and cone photoreceptors in a preclinical model of retinitis pigmentosa. This rod-specific intervention also resulted in reciprocal, decreased glycolytic activity within the retinal pigment epithThe Journal of clinical investigationAblating VHL in rod photoreceptors modulates RPE glycolysis and improves preclinical model of retinitis pigmentosa.PMC11957697TA-GT-0321-0802-COLU-TRAPR01 EY024698T32 EY013933R01 EY031324R01 EY018213R01 EY032462R24 EY028758U01EY030580,U01EY034590,R24EY028758,R24EY027285,5P30EY019007,R01EY033770,R01EY018213,R01EY024698P30 EY019007R01 EY034364R01 EY033770R24 EY027285R01 EY017863R01 EY034952R01 EY006641U01 EY034590U01 EY030580Heapes NCaruso SMLopes Da Costa BDemirkol AHass DTTsang SHCui XDu JHurley JBQuinn PMRobbings BMfalseAblating VHL in rod photoreceptors modulates RPE glycolysis and improves preclinical model of retinitis pigmentosa.Neuroretinal degenerations including retinitis pigmentosa (RP) comprise a heterogeneous collection of pathogenic mutations that ultimately result in blindness. Despite recent advances in precision medicine, therapies for rarer mutations are hindered by burdensome developmental costs. To this end, Von Hippel-Lindau (VHL) is an attractive therapeutic target to treat RP. By ablating VHL in rod photoreceptors and elevating hypoxia-inducible factor (HIF) levels, we demonstrate a path to therapeutically enhancing glycolysis independent of the underlying genetic variant that slows degeneration of both rod and cone photoreceptors in a preclinical model of retinitis pigmentosa. This rod-specific intervention also resulted in reciprocal, decreased glycolytic activity within the retinal pigment epith2025-01-01T00:00:00Z2025 Feb2026-06-01T07:46:51.408Z2025-07-09T03:04:27.868ZS-EPMC119576973993278910.1172/JCI185796