Ultrastructural changes in rat optic nerve associated with hyperphenylalaninemia induced by para-chlorophenylalanine and phenylalanine.

The morphologic effects of hyperphenylalaninemia induced by treatment with para-chlorophenylalanine (PCP) plus phenylalanine on optic nerve were studied in developing F344 rats. PCP and phenylalanine were infected daily between days 5 and 20 days of life. At 20 days optic nerve of treated animals, as compared with saline-injected controls, showed enhanced neuroglial activity with broad astrocytic septae and debris-laden oligodendrocytes. In specimens obtained long after treatment with PCP and phenylalanine, continuing gliosis with evidence of focally abnormal myelination and axonal degeneration were observed. The results are consistent with a metabolic insult sustained in early development by astrocytes and oligodendrocytes, and are considered in relation to other work in experimental hyperphenylalaninemia and to human phenylketonuria.