Anterior segment dysgenesis (ASD) is a failure of the normal development of the tissues of the anterior segment

Anterior segment

The anterior segment is the front third of the eye that includes the structures in front of the vitreous humour: the cornea, iris, ciliary body, and lens.Within the anterior segment are two fluid-filled spaces:...

 of the eye. It leads to anomalies in the structure of the mature anterior segment, associated with an increased risk of glaucoma

Glaucoma

Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...

 and corneal opacity.

Peter's (or Peters) anomaly is a specific type of mesenchymal anterior segment dysgenesis, in which there is central corneal leukoma, adhesions of the iris

Iris (anatomy)

The iris is a thin, circular structure in the eye, responsible for controlling the diameter and size of the pupils and thus the amount of light reaching the retina. "Eye color" is the color of the iris, which can be green, blue, or brown. In some cases it can be hazel , grey, violet, or even pink...

 and cornea

Cornea

The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Together with the lens, the cornea refracts light, with the cornea accounting for approximately two-thirds of the eye's total optical power. In humans, the refractive power of the cornea is...

, and abnormalities of the posterior corneal stroma, Descemet's membrane

Descemet's membrane

Descemet's membrane is the basement membrane that lies between the corneal proper substance, also called stroma, and the endothelial layer of the cornea. It is composed of a different kind of collagen than the stroma. The endothelial layer is located at the posterior of the cornea...

, corneal endothelium, lens

Lens (anatomy)

The crystalline lens is a transparent, biconvex structure in the eye that, along with the cornea, helps to refract light to be focused on the retina. The lens, by changing shape, functions to change the focal distance of the eye so that it can focus on objects at various distances, thus allowing a...

, and anterior chamber

Anterior chamber

The anterior chamber is the fluid-filled space inside the eye between the iris and the cornea's innermost surface, the endothelium. Aqueous humor is the fluid that fills the anterior chamber. Hyphema and glaucoma are two main pathologies in this area. In hyphema, blood fills the anterior chamber...

.

Pathophysiology

Several different gene mutations have been identified underlying these anomalies with the majority of ASD genes encoding transcriptional regulators

Regulation of gene expression

Gene modulation redirects here. For information on therapeutic regulation of gene expression, see therapeutic gene modulation.Regulation of gene expression includes the processes that cells and viruses use to regulate the way that the information in genes is turned into gene products...

. In this review, the role of the ASD genes, PITX2 and FOXC1, is considered in relation to the embryology of the anterior segment, the biochemical function of these proteins, and their role in development and disease aetiology. The emerging view is that these genes act in concert to specify a population of mesenchymal progenitor cells, mainly of neural crest

Neural crest

Neural crest cells are a transient, multipotent, migratory cell population unique to vertebrates that gives rise to a diverse cell lineage including melanocytes, craniofacial cartilage and bone, smooth muscle, peripheral and enteric neurons and glia....

 origin, as they migrate anteriorly around the embryonic optic cup

Optic cup

During embryonic development of the eye, the outer wall of the bulb of the optic vesicles becomes thickened and invaginated, and the bulb is thus converted into a cup, the optic cup , consisting of two strata of cells)...

. These same genes then regulate mesenchymal cell

Mesenchymal stem cell

Mesenchymal stem cells, or MSCs, are multipotent stem cells that can differentiate into a variety of cell types, including: osteoblasts , chondrocytes and adipocytes...

 differentiation to give rise to distinct anterior segment tissues. Development appears critically sensitive to gene dosage

Gene dosage

Gene dosage is the number of copies of a gene present in a cell or nucleus. An increase in gene dosage can cause higher levels of gene product if the gene is not subject to regulation from elsewhere in the body....

, and variation in the normal level of transcription factor

Transcription factor

In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...

activity causes a range of anterior segment anomalies. Interplay between PITX2 and FOXC1 in the development of different anterior segment tissues may partly explain the phenotypic variability and the genetic heterogeneity characteristic of ASD.