Chronic hypoxemia: Effects on developing nitrergic and dopaminergic amacrine cells

PURPOSE. Very low birth weight and growth-restricted children have visual i mpairments including reduced contrast sensitivity, a parameter mediated in part by dopaminergic amacrine cells. The origin of these deficits is uncert ain. In experimental fetal growth restriction, induced by placental insuffi ciency, the morphology and number of dopaminergic amacrine cells as identif ied by tyrosine hydroxylase staining were examined. In addition, the subcla ss of nitrergic amacrine cells was examined because nitric oxide released f rom nitric oxide synthase- containing neurons is proposed as a mediator of neurotoxicity and might contribute to the injury of dopaminergic amacrine c ells in this situation. METHODS. Fetal sheep were subjected to 20 or 30 days of placental embolizat ion leading to fetal hypoxemia, hypoglycemia, and growth restriction during the last third of gestation (term, approximate to 147 days). Retinal tissu e was prepared as wholemounts or cryostat sections and analyzed for retinal area, total number, density, somal size and cell process length of amacrin e cells immunoreactive for tyrosine hydroxylase or nitric oxide synthase, a nd widths of retinal layers. Retinas from fetal sheep at 72, 96, 113, and 1 40 days' gestation and adults were collected for an ontogenetic study of ty rosine hydroxylase-immunoreactive neurons. RESULTS. In growth-restricted fetuses, the number of tyrosine hydroxylase-i mmunoreactive neurons and the total length of stained processes per cell we re significantly reduced compared to control fetuses. The total number of n euronal nitric oxide synthase- containing neurons was not different between growth-restricted and control fetuses. The thickness of the inner retinal layers was reduced in hypoxemia. CONCLUSIONS. There is damage to tyrosine hydroxylase-immunoreactive amacrin e cells during fetal chronic placental insufficiency. This damage might be involved in the altered retinal dopaminergic system observed in very low bi rth weight infants, some of whom are growth-restricted. Furthermore, a diff erential susceptibility of tyrosine hydroxylase-immunoreactive and neuronal nitric oxide synthase-containing amacrine cells to hypoxemic injury has be en demonstrated. These observations add to the current hypothesis that neur onal nitric oxide synthase- containing neurons are resistant to hypoxemic i njury and may be involved in mediating some of the neuronal damage that res ults from hypoxemic insults.