While glucose metabolism has been extensively studied in photoreceptors, the role of other metabolic pathways in sustaining their health remains underexplored. A new study published recently in eLife has identified glutamine (Gln) catabolism, initiated by glutaminase (GLS), as a crucial metabolic process for rod photoreceptor survival and function.
The University of Michigan researchers generated rod-specific GLS knockout (cKO) mice and inducible knockout models targeting mature photoreceptors. Using in vivo optical coherence tomography (OCT), electroretinography (ERG), metabolomics, and stable isotope tracing, they examined the structural, functional, and biochemical consequences of GLS loss.
The University of Michigan researchers generated rod-specific GLS knockout (cKO) mice and inducible knockout models targeting mature photoreceptors. Using in vivo optical coherence tomography (OCT), electroretinography (ERG), metabolomics, and stable isotope tracing, they examined the structural, functional, and biochemical consequences of GLS loss.
A key finding of the team was that GLS deletion in rods led to rapid and profound degeneration, with significant thinning of the outer nuclear layer by postnatal day 21 and near-complete photoreceptor loss by day 84. ERG recordings revealed marked declines in scotopic a- and b-wave amplitudes, alongside secondary cone degeneration. Notably, GLS was shown to be essential not only during photoreceptor development, but also for the maintenance of mature cells.
The study positions glutamine catabolism as a central metabolic pathway in rod photoreceptors, supporting biomass production, redox homeostasis, and resistance to stress-induced apoptosis. Beyond glucose, glutamine metabolism emerges as a vital determinant of photoreceptor health. Targeting this pathway could yield innovative neuroprotective strategies for conditions such as retinitis pigmentosa and age-related retinal degeneration, meriting further translational research.
