Update on Anterior Segment Development with Emphasis on Genetics and Correlation with Pathogenesis of Developmental & Primary Open Angle Glaucoma

Abstract

The ocular anterior segment structures are derived from periocular mesenchyme, which consists of neural crest cells and cranial paraxial mesoderm. Many embryological facts have been developed based on the fates of neural crest and mesoderm in mice and in chick. The interactions between the ocular mesenchyme and the surface ectoderm derived cells are also essential for the coordination of anterior segment development. These interactions are mediated by several transcription factors expressed in both the epithelial and mesenchymal cells and are being extensively studied. Anterior Segment dysgenesis (ASD) is a spectrum of disorders of variable phenotypic expressions caused by abnormal migration and differentiation of neural crest cells. Patients with ASD are susceptible to develop infantile glaucoma, congenital endothelial dystrophy, sclerocornea and aniridia. There has been an evident overlapping observation in the genetic mutations between the ASD phenotypic spectrum and glaucoma especially the primary congenital glaucoma (PCG) since it involves abnormal development of Schlemm's canal and the drainage structures. In this review, we are highlighting the steps in the embryological development of the anterior segment chamber structures. We also present the role of various transcription factors and link the above information to some of the genetic abnormalities, which are known in association with the pathogenesis of glaucoma.

Demographics and histopathological characteristics of enucleated microphthalmic globes

“…Disruption of this embryogenesis as well as failure of formation of optic vesicles can lead to multiple ocular congenital anomalies 11 , 12 . The migrating waves of the neural crest from the edge of the neural tube are involved in anterior segment development, and similarly, specific interactions as well as the principles of induction and influence of one developing ocular structure on the growth of another are involved and mediated by epithelial and/or mesenchymal transcription factors, which are the basis behind the genetic background of eye anomalies 13 .…”

Anterior segment dysmorphogenesis of the eye and glaucoma in MG-W gerbils

“…Neural crest cells contribute to the development of the corneal endothelium and stroma, sclera, iris stroma, ciliary muscle, process, zonule and body, trabecular meshwork, canal of Schlemm, and pericytes of the ocular blood vasculature 9 , 10 , 11 . Anterior segment mesenchymal dysgenesis in humans encompasses a group of developmental disorders of the eye caused by abnormal neural crest cell migration and differentiation 12 , and is frequently associated with iris hypoplasia, synechia, enlarged corneal diameter, ectopia lentis, and abnormal development of the trabecular meshwork and canal of Schlemm, with subsequent glaucoma 9 , 12 , 13 . The lens undergoes morphological alterations with posterior dislocation 14 .…”

“…This finding strongly suggests that the primary lesions in the present cases were consistent with anterior segment congenital anomalies associated with inadequate neural crest migration or differentiation. A number of genes are involved in anterior segment mesenchymal dysgenesis 10 , 12 , 13 . Genomic alteration cannot entirely be ruled out in the present cases.…”