ArticlebioRxiv : the preprint server for biology2026
AAV-mediated age- and circuit-dependent restoration of photoreceptor synaptic structure and function in α2δ4-associated retinal synaptopathy.
Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
Purpose: Synaptic dysfunction and neurite remodeling are early features of many inherited retinal diseases, but whether synaptic function can be restored after circuit remodeling remains unclear. We evaluated the therapeutic potential of adeno-associated virus (AAV)-mediated α2δ4 gene supplementation in a mouse model of Methods: AAV8-GRK1-α2δ4 was delivered by subretinal injection to α2δ4 knockout mice at neonatal, young adult, or middle-aged adult stages. Retinal function was assessed by electroretinography. Synaptic organization and circuit remodeling were evaluated by immunohistochemistry. Results: AAV-mediated α2δ4 expression restored synaptic localization of Cav1.4, ELFN proteins, and mGluR6 at all treatment ages. However, circuit structure and functional rescue were age- and circuit-dependent. Neonatal treatment restored rod and cone transmission and prevented photoreceptor terminal retraction and bipolar cell dendritic sprouting. Rescue in young adults improved rod and cone circuit function but did not reverse neurite remodeling. Rescue in middle-aged mice restored cone but not rod transmission. Notably, neonatal treatment produced the highest proportion of synapses within synaptic layer, whereas adult treatment generated increasing ectopic synapses in nuclear layer. Conclusions: Photoreceptor synaptic assembly remains plastic in remodeled retinas and can be restored by α2δ4 supplementation. However, rescue efficacy is influenced by age and circuits with rod circuits exhibiting a narrower therapeutic window. Synaptic molecular reassembly can occur without neurite restoration. These findings establish α2δ4 gene therapy as a promising treatment for
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.