Abnormal development of the retinogeniculate projection in Siamese cats

Abstract

In the visual system of Siamese cats, the lateral geniculate nucleus (LGN) receives an abnormally large projection from the contralateral eye and a correspondingly reduced projection from the ipsilateral eye. In order to determine how this abnormal pattern of retinal input arises, the prenatal development of the retinogeniculate projection was studied in Siamese cats using the anterograde transport of intraocularly injected [3H]leucine and horseradish peroxidase. Labeled axons from the ipsilateral eye can be detected in the optic tract by embryonic day 30 (E30; gestation is 65 days), several days later than found in normally pigmented animals. The ipsilateral projection is not only apparently delayed but also is reduced in size as compared with normal animals, and this reduction persists throughout development, indicating that the Siamese mutation acts to misdirect growing optic axons to the contralateral side of the brain as originally proposed (Guillery, R. W. (1969) Brain Res. 14: 739–741). The effect of an altered retinal projection on the ingrowth and segregation of retinal fibers to the LGN was also examined. In Siamese fetuses, not until E41 can significant label be seen within the ipsilateral LGN as compared to E35 in normally pigmented fetuses. As in normal animals, in Siamese fetuses, also, the labeled retinogeniculate afferents from the two eyes initially overlap within regions of the LGN before segregating into layers. However, measurements of the area occupied by labeled afferents from the ipsilateral and contralateral eyes indicate that maximum overlap of the two sets of afferents, although close to normal in amount, does not occur until about E51--again several days later than in normally pigmented animals (E47). The time course of segregation is also altered in Siamese cats. The onset of segregation, as signaled by the removal of contralateral eye afferents from territory destined for the ipsilateral eye and by the restriction of ipsilateral eye afferents, does not occur until about E51 in Siamese cats as compared with E47 in normally pigmented animals. Despite this delay in onset, the final segregation of the two sets of afferents in Siamese cats reaches adult-like levels at about the normal time. Thus, the misrouting of axons at the optic chiasm in Siamese cats not only alters the final pattern of innervation from the two eyes within the LGN, but also delays the onset and shortens the total duration of segregation itself.