Mouse rod photoreceptors: GOT1 versus GOT2 loss during aging and stress
In mice, removing Got1 from rod photoreceptors caused degeneration linked to NADH accumulation, while removing Got2 caused minimal degeneration; lowering GOT2 appeared neuroprotective after experimental retinal detachment. [1]
Automatic summary · not editorially reviewed
The key findings
Mice lacking Got1 only in rod photoreceptors showed photoreceptor degeneration with NADH accumulation and a lower retinal NAD/NADH ratio. [1]
In Got1 knockout mice, increased NADH oxidation prolonged photoreceptor survival, which the authors link to reductive stress as a driver. [1]
Loss of Got2 in photoreceptors was neuroprotective after experimental retinal detachment, and GOT2 was decreased in several degeneration models. [1]
The source at a glance
- Study type / format
- Preclinical mouse study using conditional knockout models (abstract).
- Population / context
- Rod photoreceptors in mice, including models of retinal detachment and photoreceptor degeneration.
- Summary based on
- Study abstract
- Original publication
- June 18, 2026
Rod-specific Got1 and Got2 knockout mice
The authors studied rod photoreceptors, the light-sensing cells whose loss causes vision loss in many blinding diseases. They generated mice in which either Got1 or Got2 was removed only in rod photoreceptors (conditional knockout). GOT1 sits in the cytosol and GOT2 in mitochondria; both are parts of the malate-aspartate shuttle, which moves reducing equivalents from cytosol to mitochondria. Earlier work by the group had shown that Got1 loss causes photoreceptor degeneration together with NADH accumulation and a lower retinal NAD/NADH ratio.
Supporting source [1]
Opposite NADH effects of Got1 versus Got2 loss
Boosting NADH oxidation, by metabolic or genetic means, prolonged photoreceptor survival in Got1 knockout animals, which the authors interpret as evidence that NADH accumulation, or reductive stress, drives the degeneration. In contrast, Got2 knockout caused minimal photoreceptor degeneration and shifted retinal NADH and the NAD/NADH ratio in the direction opposite to reductive stress. GOT2, but not GOT1, was decreased in several models of photoreceptor degeneration, including retinal detachment, where the NAD/NADH ratio favours a reductive state. Losing Got2 in photoreceptors was neuroprotective after experimental retinal detachment, suggesting lower GOT2 may be part of a stress response that promotes photoreceptor survival.
Supporting source [1]
Mouse evidence, not a treatment for patients
The work compares two rod-specific gene deletions in mice and reports survival and NAD/NADH measurements in degeneration models. It describes GOT2 as a potential therapeutic target, but no human treatment, dosing or clinical benefit was tested. The abstract does not report sample sizes, follow-up periods or how long the animals were observed.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. Findings come from mouse models with rod-specific gene deletions and experimental retinal detachment, not from human studies. Sample sizes, follow-up and observation periods are not reported in the abstract. GOT2 is described as a potential target, not a validated therapy.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Chen M, Weh E, Goswami MT, Weh KM, Hager H, Sajjakulnukit P, Weingarten AJ, Subramanya S, Miller N, Chaudhury S, Piraino E, Chandel NS, Ryals RC, Lyssiotis CA, Wubben TJ. · europepmc.org · June 18, 2026