bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2025.10.23.683644

Turquoise killifish naturally develop hallmarks of age-related macular degeneration with advancing age

Noel, N. C.·Breitenbach, E.-M.·MacDonald, R. B.
View original source ↗Export metadata ↓

Abstract

Ageing is a major risk factor for developing vision loss diseases such as age-related macular degeneration (AMD). Unfortunately, we do not have the ability to effectively prevent, slow, or stop onset and progression of AMD long term. These challenges with therapeutic development result from poor understanding of disease mechanism and pathogenesis due to a lack of animal models that manifest the hallmark features of disease. Here, we investigated the rapidly ageing turquoise killifish (Nothobranchius furzeri) retina for features of human ageing and AMD. We report that the ageing killifish retina expresses genes associated with human retinal disease in the photoreceptors and retinal pigment epithelium (RPE). Our characterisation of the retina identified that killifish spontaneously develop many hallmark features of AMD and human ageing, including photoreceptor deterioration, lipid deposits, outer retinal inflammation, and ceramide accumulation in the RPE with advancing age. Further, we identify a sex-specific difference in the severity of phenotypes. We propose that the turquoise killifish is a highly suitable model for investigating ageing and AMD-related disease mechanisms across the lifespan.

Explore related subjects

neurosciencePreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Noel, N. C., Breitenbach, E.-M., MacDonald, R. B.. 2025-10-24. Turquoise killifish naturally develop hallmarks of age-related macular degeneration with advancing age. https://doi.org/10.1101/2025.10.23.683644

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Rab10 and Arhgef7 interact to promote axon extension by linking vesicle supply and exocytosis

The formation of functional neural circuits begins with the extension of a single axon by immature neurons. Axon elongation requires an expansion of the plasma membrane that depends on the polarization of vesicle trafficking and exocytosis. It is not completely understood how the increased transport of vesicles into the growing axon is linked to their subsequent insertion into the plasma membrane. An analysis of early stages of neuronal differentiation indicates that an asymmetry in neurite length precedes axon specification and the accumulation of PPVs in the nascent axon. We show that increasing the transport of vesicles in unpolarized neurons is sufficient to promote the extension of additional axons. This effect indicates that an increased supply of vesicles stimulates their subsequent insertion into the membrane to allow neurite growth. The link between vesicle transport and exocytosis is mediated by the interaction of Rab10 with Arhgef7. Rab10 stimulates Arhgef7 activity on PPVs as a GEF for Cdc42b to promote axon extension through exocyst-dependent exocytosis, suggesting that their interaction links the increased supply of PPVs to their exocytosis.

neuroscience↗
bioRxiv2026

Subcellular Spatial Profiling Unveils Links Between Neuritic Plaques with Selective Tau Vulnerability in Alzheimer's Disease

Alzheimer's disease (AD) features widespread extracellular amyloid-{beta} plaques but selective intraneuronal tau accumulation in cortical layers II/III and V, while layer IV remains relatively resistant. Here, we combined subcellular spatial transcriptomics with co-registered A{beta} and pTau immunohistochemistry to determine why neurons exposed to comparable plaque-associated pathology differ in somatic pTau accumulation. Plaque-associated neuritic stress occurred similarly across layers, but layer IV neurons showed attenuated pTau accumulation and reduced somatic expression of a shared neurite-soma stress program involving DCTN1, CALM3, NORAD, and PIN1. Trajectory analysis within layers identified tau-vulnerable and resistant neuronal states implicating calcium signaling, retrograde transport, and lysosomal function. Notably, astrocytic APOE-neuronal LRP1 co-expression increased significantly along the pTau-vulnerable trajectory, and APOE {epsilon}4 was associated with stronger coupling of local plaque pathology to pTau-associated molecular programs. These findings reveal neuronal programs and neuron-glia interactions underlying selective tau vulnerability and resistance in AD, highlighting potential tau-targeting therapeutics.

neuroscience↗
bioRxiv2026

Widespread oscillatory suppression in autism persists in the absence of psychotropic medication.

Purpose: Investigate the neural oscillatory activity associated with autism spectrum disorder (ASD) using electroencephalographic (EEG) recordings in children and adolescents. Compare the corresponding oscillatory power between ASD patients taking psychotropic medication with a drug-naive group. Methods: ASD diagnosis was done using DSM-IV and CARS (Childhood Autism Rating Scale). EEG recordings employed 22 scalp electrodes (10/20 system). ASD vs. neurotypical groups were matched for sex and age (5 females; average age: ~10 years old). We analyzed the resting state (eyes open) EEG power spectrum during ~2-minute recordings. The multitaper FFT method was used to estimate spectral power for the delta, theta, alpha, beta and gamma frequency bands. We pooled together data from several electrodes to compute comprehensive power spectra and assess the oscillatory behavior of macro brain regions. Results: We observed widespread (~4Hz - 20Hz) oscillatory suppression comprising the theta, alpha and beta frequency bands. The most widespread and robust ASD-associated power suppression was in the high theta and alpha bands. Delta and gamma bands showed no significant power change for any of the brain regions studied. Results from a subgroup of patients (N = 9) who never used psychotropics confirmed these findings, indicating that they are not an artifact of medication. Conclusion: Suppression in theta, alpha and beta oscillations may offer insights into the neurophysiological underpinnings of autism and could be used as an accessible and comprehensive tool in ASD diagnosis, regardless of the patients being or not on medication.

neuroscience↗