Exposures to low-dose of bisphenol A during perinatal retinal development

Abstract

Purpose : Our environment is continuously enriched in pollutants that contribute to increase the prevalence of diseases or even the emergence of new pathologies. The effects of chronic low-doses exposure to endocrine disruptors (EDs) on the retina remain unclear. Bisphenol A (BPA) is an ED widely used in the production of polycarbonate plastics leading to organ dysfunction and/or cancers. The aim of this study is to assess the effect of BPA on retina following low-dose perinatal exposure and to elucidate underlying mechanism of action.

Methods : Five µg/kg of BPA was administered to 5-day-pregnant rats 3 times a week. At weaning day 21, newborns received the same dose of BPA until post-natal day 30. Eyes were collected for histology, immunohistochemistry and transcriptomic analysis.

Results : No alteration in the retina structure was noticed by histology. However, a statistically significant modification in the thickness of the inner plexiform layer and the outer nuclear layer were noted (respectively -24% and +12%). Quantification of retinal cells using specific markers demonstrated a statistically significant increase in the number of cones (11.7 %) and a decrease in the number of bipolar cells and retinal ganglion cells (respectively, 21.3% and 10.4%). The number of amacrine and horizontal cells were unmodified. Pre-synaptic dendrites of bipolar cells displaying length reduction with BPA treatment, all synaptic vesicles were stained with synaptophysin. The vesicles distribution in the ONL increased up to 57.2% in BPA condition. Transcripts analysis revealed 1,395 genes significantly regulated in BPA retina compared to control (p≥0.05; FD±1.2). Canonical ingenuity pathways analysis showed significatively regulation of pathways involved in cell-cell junctions, neurogenesis, hormones signaling, protein G signaling, visual cycle, responses to neurotransmitters and to hypoxia. Androgen signaling, G beta Gamma signaling and dopamine receptor signaling pathways were significatively activated (Z-score >2).

Conclusions : Our results show that low-dose perinatal exposure of BPA induce slight modifications of the cones-bipolar-retinal ganglion cells ways network, corroborated by the wide transcriptional pathways variations. In conclusion, BPA induces slight retinal cell modifications which may contribute to increase the prevalence of neurodegenerative diseases.

This is a 2021 ARVO Annual Meeting abstract.