Ophthalmologic findings in an induced model of Holoprosencephaly in zebrafish

Early forebrain development is a fascinating process. The fate of brain function but also the fate of visual perception largely depends on it. Holoprosencephaly (HPE) is the most frequent developmental disorder of the forebrain, during which the separation of the early precursor domains is hampered. A spectrum of clinical manifestations is seen with severe forms like alobar HPE and less severe forms like lobar HPE. The ophthalmologic findings which accompany HPE are also found as a spectrum that ranges from ocular hypotelorism and synophthalmia to cyclopia and anophthalmia. Here we ask, whether anophthalmia or cyclopia is the default ophthalmologic finding in severe forms of HPE. In this brief analysis, we made use of a recently established zebrafish model of severe HPE, based on BMP ligand induction. Such BMP ligand induction resulted in anophthalmia. We attenuated the induction protocol to investigate whether the anophthalmia phenotype could be changed into a cyclopic phenotype. We found a spectrum of ocular phenotypes, ocular hypotelorism, and also cases of synophthalmia and cyclopia. This suggests that in the context of this HPE model the strongest ophthalmologic phenotype is anophthalmia and less severe forms are cyclopia, synophthalmia and ocular hypotelorism.