Year: 2026
Type: preprint
Abstract: Valproic acid (VPA) is a widely used antiepileptic drug that also increases the risk of neurodevelopmental disorders in the offspring of exposed mothers. Prenatal exposure to VPA is a widely used rodent model of autism spectrum disorder (ASD). Anatomical, functional and molecular alterations in the retinas of various ASD model animals have been described, but the impact on the neural composition of the retina remains unclear. We examined whether the density and spatial regularity of selected retinal neuron populations are altered in the VPA induced model of ASD. Whole-mount retinas of 2-month-old VPA-treated and control animals were immunolabeled for S-cones, horizontal cells, AII amacrine cells, and parvalbumin-positive wide-field amacrine cells (PV-wfACs), and the positions of labelled cells mapped in various regions of interest across the retina. Multivariate analysis of the densities of the four cell types was used to identify latent factors accounting for their covariance structure. The first principal component was identified as a measure of retinal centrality and used to adjust for retinal location when testing for treatment effects. Linear mixed-effects modeling revealed a 9% decrease in AII amacrine cell density and a 12% increase in PV-wfACs density in VPA-model animals. Regularity indices calculated from nearest neighbor distances or Voronoi-domain areas of cell mosaics were largely unchanged. These findings suggest that prenatal VPA exposure selectively alters the cellular composition of inhibitory inner retinal circuitry in the rat ASD model, while leaving the self-organizing mechanisms responsible for retinal spatial order largely intact. Lay Summary Valproic acid (VPA) is a medicine for epilepsy, but it can also raise the risk of autism in children when taken during pregnancy. In rats exposed to VPA before birth, we found changes in certain nerve cells of the retina: one type of cell important for night vision was reduced, while another type increased slightly, while most other cells stayed the same. This suggests that the changes in development that lead to autism may also be reflected in the structure and function of the eye.
Institution: University of Pecs
Language: English
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7165167945