Glaucoma is a heterogeneous group of diseases that is currently considered to be the leading cause of irreversible blindness worldwide. Of the identified risk factors, elevated intraocular pressure remains the only modifiable risk factor that can be targeted clinically. Ocular hypertension is often a result of dysregulation of aqueous humour fluid dynamics in the anterior eye segment. Aqueous humour drainage is regulated by structures located in the anterior chamber of the eye. In some circumstances dysregulation occurs due to developmental abnormalities of these structures. The malformation of structures in the anterior segment is thought to be due to a defect in the differentiation and/or migration of the periocular mesenchyme during development. Unique to vertebrates, the neural crest cell (NCC) population contributes to the periocular mesenchyme and is instrumental to the proper development of structures in the anterior segment. For many years our laboratory has examined the role of the Activating Protein-2 (AP-2) transcription factors that are expressed in the neural crest and vital during the development of the eye. The purpose of this research project is to investigate the role of AP-2β in the NCC population during the development of the anterior segment of the eye. Conditional deletion of AP-2β expression in the NCC population demonstrated that mutants have dysgenesis of structures in the anterior segment including defects of the corneal endothelium, corneal stroma, ciliary body and a closed iridocorneal angle. Loss of retinal ganglion cells and their axons was also observed, likely due to the disruption of aqueous outflow, suggesting the development of glaucoma. The data generated from this research project will be critical in elucidating the role of AP-2β in the genetic cascade dictating the development of the anterior eye segment in addition to providing scientific research with a novel model of glaucomatous optic neuropathy. / Thesis / Master of Science (MSc)

The main functional cells of the inner ear are neurons and sensory cells that are formed from a common embryonic epithelial neurosensory domain. Discovering genes important for specification and differentiation of sensory cells and neurons in the inner ear is a crucial basis for understanding the pathophysiology of hearing loss. Some of these factors are necessary not only for the inner ear but also for the development of other neurosensory systems such as the visual and olfactory system. The aim of this work was to reveal functions of transcription factor SOX2 in inner ear development by using mouse models with different conditional deletions of Sox2 gene. Sox2 gene was deleted by cre-loxP recombination. In Isl1-cre, Sox2 CKO mutant, reduced number of hair cells differentiated only in some inner ear organs (utricle, saccule and cochlear base) and not in others (cristae and cochlear apex). Early forming inner ear neurons in the vestibular ganglion and neurons innervating the cochlear base developed in these mutants but died by apoptosis due to the lack of neurotrophic support from sensory cells. Late forming neurons in the cochlear apex never formed. In Foxg1-cre, Sox2 CKO mutant, only rudimental ear with no sensory cells was formed. The initial formation of vestibular ganglion with peripheral and...