Effects of maternal phenylketonuria on the development of the offspring's eye

Phenylketonuria (PKU) is an autosomal recessive disease caused by phenylalanine-4-hydroxylase (P-4-H) deficiency, which is a liver-specific enzyme that catalyzes the hydroxylation of l-phenylalanine (Phe) to l-tyrosine (Tyr). The deficiency of this enzyme leads to the accumulation of Phe in the tissues and plasma of patients. Among the clinical symptoms of this disease are mental retardation and other neurological features. The mechanisms of retinal cell damage are still poorly understood. In order to evaluate the damage in offspring of PKU mothers, fifty pregnant rats were used and arranged into two main groups, i.e., a control group and a group consisting of rats with experimentally induced PKU. Induction of PKU was carried out by daily intragastrical administration of 30 mg DL–alpha methylphenylalanine/150 g b.w. plus 60 mg/kg b.w. Phe at 12 h intervals throughout pregnancy till parturition as well as throughout lactation period till 14 days post-partum. Morphometric analysis of retina in 1, 7 and 14-day-old pups of PKU mothers revealed a marked reduction of retinal thickness. Histological observations revealed numerical reduction of pigment cells. Apoptic cell death of retinal pigment cells, and of nuclear layer and ganglionic cells were observed. The nerve layer showed apparent vacuolar degeneration. At transmission electron microscope (TEM) level, pigment epithelium showed distortion of apical microvilli, vacuolation of cytoplasm and reduction of cytoplasm organelles. The Brush's membrane showed apparent thickening. In 7-day-old pups of PKU mothers, photoreceptor inner segment showed apparent degeneration. In 14-day-old pups of PKU mothers, both the inner and outer photoreceptor segment were degenerated and the stacked membrane of the outer segment appeared vacuolated and degenerated.