Analysis Of Ocular Phenotype In CYP1B1-null Mice

PartⅠStructural observation of the anterior chamber angle in CYP1B1-null miceObjective To determine the influence of CYP1B1 gene on the structure of anterior chamber angle in mice.Methods Adult CYP1B1-null mice were used, with the comparison of C57BL/6J mice as control. The eyes were plastic-embedded and the anterior chamber angle were sagittally sectioned at 3μm thickness. The morphology and structure of these tissues was studied by light microscopy and transmission electron microscopy.Results The anterior chamber angle in C57BL/6J mice was well developed. But in CYP1B1-null mice, a varity of anomalies were found in the these tissues, including hypoplastic and compressed trabecular meshwork,abnormal structure of trabecular cells, a basal lamina extending from the cornea over the meshwork, small or absent Schlemm's canal, and long iris process extending from the iris root to the trabecular meshwork. These pathological changes exsited focally and the rest of the angle were normal.Conclusion CYP1B1 gene plays an important role in the development of the anterior chamber angle. Deletion of this gene leads to the abnormalities in trabecular meshwork, Schlemm's canal and iris process, which may have some influence on the metabolism and function of the outflow facilities.PartⅡStudy of retinal damage in CYP1B1-null miceObjective To explore whether retinal damage existed in the CYP1B1-null mice, and its relationship with anterior chamber angle development.Methods Adult CYP1B1-null mice were studied with C57BL/6J mice as control. The morphology and structure of the anterior chamber angle, the retina and the optic nerve were studied by light microscopy and transmission electron microscopy. The apoptosis of the retinal cells was assayed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling(TUNEL).Results In the 18 observed C57BL/6J mice, no damage in the retina and the optic nerve and no dysgenesis in the anterior chamber angle were found. In the 18 CYP1B1-null mice, 7 eyes had retinal damage: moderate degeneration of optic nerve by light microscopy, progressive condensation and shrinkage of the nuclei of the retinal ganglion cells by electron microscopy and increased TUNEL-positive cells in the ganglion cell layer and inner nuclear layer by TUNEL staining after compare with the control group. Moreover, ocular drainage system dysgenesis was found in all the 7 eyes.Conclusion CYP1B1 gene deletion would lead to the dysgenesis of ocular drainage system and the damage in retina and optical nerves. These damage in the retina and the optic nerve was in a positive correspondence to the degree of ocular drainage system dysgenesis.