Prenatal cigarette smoke exposure increases vulnerability to chronic retinal hypoperfusion in adult rats.

Abstract

BACKGROUND: Numerous studies indicate that smoking during pregnancy has harmful effects on the offspring. Prenatal smoke exposure (PSE) may lead to fetal hypoxia and ischemia, which negatively affect brain development and increase the risk of neurological deficits. However, its long‑term impact on retinal vulnerability in adulthood is less well understood. OBJECTIVE: To investigate the effects of prenatal smoke exposure on retinal structure and vulnerability in a chronic retinal hypoperfusion model in adult rats. METHODS: Wistar rats were mated and exposed to whole‑body tobacco smoke for 2 hours daily from mating until delivery, using a closed‑chamber manual smoking system with four research cigarettes per occasion, modelling passive smoking. Neurobehavioral development was assessed in newborn rats during the first weeks of life. At 5 months of age, permanent bilateral common carotid artery occlusion (BCCAO) was performed under isoflurane anaesthesia via midline neck incision. Two weeks after BCCAO, all animals were sacrificed with an overdose of anaesthetic, and eyes were processed for histological analysis. Retinal layer thickness (outer and inner nuclear and plexiform layers) and cell counts per 100 µm in the ganglion cell layer (GCL) were measured. RESULTS: BCCAO resulted in markedly reduced retinal layer thickness and morphological signs of degeneration with individual variation in all layers compared to sham‑operated controls. The number of cells in the GCL decreased by approximately 50%. Prenatal smoke exposure alone also led to a significant reduction in GCL cell number. While our previous work had shown only minor retardation of neurobehavioral development in prenatally smoke‑exposed neonatal rats, the present study demonstrated pronounced histological damage in the retina of adult rats subjected to PSE, with further exacerbation after chronic hypoperfusion. CONCLUSIONS: Prenatal exposure to tobacco smoke induces long‑lasting structural alterations in the retina and increases susceptibility to later hypoperfusion‑induced retinal injury in adult rats. These findings support the concept that adverse intrauterine exposures have persistent consequences for neural tissues and underscore the importance of avoiding smoking during pregnancy.