Scientists identify genetic factors shaping retinal degeneration and their broader implications for neurodegeneration.
A study published in Molecular Neurodegeneration has highlighted how genetic background significantly influences the aging and degeneration of the retina, with potential implications for understanding brain health and neurodegenerative diseases. The research, which was conducted at The Jackson Laboratory, examined molecular aging signatures across genetically diverse mouse strains, identifying key genetic determinants of susceptibility to age-related retinal degeneration.
Longevity.Technology: The potential applications of this research are diverse; identifying and validating WSB and NZO mice as improved preclinical models for common retinal neurodegenerative diseases could facilitate the testing of interventions aimed at preventing or slowing age-related retinal degeneration. The multi-omics approach used in the study highlights the potential for identifying therapeutic targets, particularly for age-related conditions affecting both the retina and the brain. Additionally, these findings contribute to the growing interest in using the retina as a biomarker for neurodegenerative processes, potentially aiding in the early detection and treatment of diseases such as Alzheimer’s. A greater emphasis on genetic diversity in aging research may also pave the way for more personalized approaches to neurodegenerative disease treatment, tailoring interventions based on an individual’s genetic susceptibility.
Genetic diversity shapes retinal aging
The retina shares many biological similarities with the brain, making it a valuable model for studying neurodegeneration. This study analyzed nine genetically distinct mouse strains using transcriptomic and proteomic approaches to determine how genetic context modulates retinal aging. The findings indicate that genetic differences strongly influence the molecular signatures of aging, impacting retinal cell function and survival.
Researchers observed that two specific strains – WSB/EiJ and NZO/HlLtJ – exhibited pronounced age-related retinal degeneration. WSB mice showed significant photoreceptor dysfunction, with early-onset abnormalities reminiscent of human retinitis pigmentosa, while NZO mice displayed vascular and neuronal changes consistent with diabetic retinopathy. Both strains demonstrated human-relevant retinal pathologies, positioning them as improved preclinical models for age-related neurodegenerative diseases [1].
“It was promising to see that the molecular data we generated predicted specific retinal cell abnormalities in these two strains,” said Olivia Marola, a JAX postdoctoral associate and co-first author of the new paper. “When we saw unique changes in NZO’s retinal ganglion cells at the molecular level, sure enough, we saw drastic functional changes in those cells [2].”
“The challenge in studying age-related eye diseases is that aging is heterogeneous,” said Gareth Howell, professor and Diana Davis Spencer Foundation Chair for Glaucoma Research at JAX, who led the research. “Observing how aging occurs in one strain of mice might not be relevant to all mice – or humans. To overcome the limitations of previous studies, we wanted to know how genetic context drives aging of the retina [2].”
Molecular insights into age-related retinal degeneration
Using transcriptomics and proteomics, the study identified genetic signatures associated with photoreceptor function, immune activation and metabolic processes. Age-related loss of retinal ganglion cells and photoreceptors varied significantly between genetic backgrounds, suggesting that some individuals may be inherently more susceptible to retinal degeneration due to their genetic makeup.
WSB mice exhibited early photoreceptor dysfunction, which progressed to extensive loss of these cells with age. Proteomic analysis suggested that reduced expression of key mitochondrial and ciliary proteins might underlie this degeneration. Conversely, NZO mice showed progressive loss of retinal ganglion cells, a process linked to oxidative stress and vascular dysfunction. These findings reinforce the view that genetic predisposition plays a crucial role in determining susceptibility to retinal and possibly brain neurodegeneration.
Potential implications for brain health
The study’s findings have broader significance for neurological research, as retinal aging is often linked to neurodegenerative conditions such as Alzheimer’s and Parkinson’s disease. The researchers suggest that insights from retinal studies could inform strategies for identifying biomarkers and therapeutic targets for neurodegeneration in the brain.
Gareth Howell, senior author of the study, emphasized the importance of genetic diversity in research. “The genetic background of an individual influences their susceptibility to neurodegeneration,” he said. “By studying the aging retina in genetically diverse models, we can better understand the molecular underpinnings of neurodegenerative diseases [2].”
[1] https://molecularneurodegeneration.biomedcentral.com/articles/10.1186/s13024-025-00800-9
[2] https://www.jax.org/news-and-insights/2025/february/new-study-uncovers-how-genes-influence-retinal-aging-and-brain-health
