Cataracts are the most common cause of blindness worldwide  and a very significant cause of visual impairment in infants and children.

Congenital cataracts are seen in 10 to 60/100,000 births in the United Kingdom and in 50 to 150/100,000 births in developing countries.

Identifying the genetic variants causing congenital cataracts has not only improved our understanding of the pathogenesis of infantile cataracts, the most frequent treatable cause of childhood blindness, but also their more common counterpart, adult-onset cataracts.

Lens development
The ocular lens provides a unique model for understanding the inductive interaction of various embryonic tissues, as well as cell differentiation, signaling, proliferation, physiology, biochemistry, longevity, and organelle degradation.

The structure is surrounded by a thick capsule and filled with elongated lens epithelial cells (LECs) that have differentiated into lens fiber cells.

The lens is the only organ that continually evolves and increases in size without replacing any cell in its system.

It performs its role to refract light onto the retina until mutation or the effects of aging, the environment, or intrauterine infections compromise its transparency and optical function.

Such insults cause changes to the biomolecules and trigger homeostatic imbalance in the lens, leading to protein aggregation and cataracts, thus increasing light scatter to affect refraction and cause loss of vision.

Lens development is a result of a series of inductive events during eye morphogenesis. The eye begins to develop during gastrulation at the beginning of week 4 (day 22, Carnegie stage 9).

A single eye field (eye primordium) arises in the middle of the anterior neural plate (diencephalon region of the developing brain), which separates into 2 optic vesicles and induces the overlying surface ectoderm to form the lens placode (lens primordium) by day 28 (Carnegie stages 12-13).

During this stage, a series of inductive interactions begin to shape the eye, driven by signaling molecules such as bone morphogenetic proteins and fibroblastic growth factor 2, and by eye field transcription factors including PAX6, RAX, SIX3, and LHX2.

The lens placode invaginates to form the cup-shaped lens pit, which makes a complete circle of cells and separates from the surface ectoderm to develop into the lens vesicle.

The portion of the optic vesicle that faced the lens placode gives rise to the retina. The retina, in turn, provides oxygen and inductive signals that regulate the growth and apical-posterior axis of the lens.

This tissue integration continues to enable the functional optimization of eye function with the establishment of emmetropia.

In the early optic cup stage, the lens vesicle releases signals that induce the overlying surface ectoderm to differentiate into the corneal epithelium.

After the lens vesicle has closed (weeks 4-5; Carnegie stage 15), secondary fiber cells add to the growing lens as the fetal nucleus starts to form in weeks 6 to 7 (Carnegie stages 16-19), derived from the epithelial cells located at the equator of the developing lens.

Around week 8 (Carnegie stage 20), the Y-shaped suture appears at the anterior and posterior poles of the embryonic nucleus of the lens, as the terminal ends of the secondary lens fibers abut each other.

Congenital cataracts
Childhood cataracts may occur in isolation associated with other ocular abnormalities, such as anterior segment mesenchymal dysgenesis due to variants in transcription or development factors, or be a part of multisystem genetic disorders.

Nearly half of congenital cataracts are characterized as inherited and they are a clinical feature of almost 200 syndromic genetic diseases. Cataract was the first autosomal disease to be genetically mapped in humans following its identification at the start of the 20th century. 

Since then, congenital cataracts have been shown to be associated with considerable genetic and phenotypic heterogeneity.

Mode of inheritance
Most (57.5%) inherited cataracts are autosomal dominant (AD) with complete penetrance but variable expression; autosomal recessive (AR; 21.4%) and X-linked (XL; 6.2%) inheritance cataracts are less frequent.¹²

Several distinct phenotypes of congenital cataract exist, defined mainly by the timing, position (embryonic, fetal, or cortical), and appearance (nuclear, cortical, complete, blue-dot, anterior polar, posterior polar, pulverulent, lamellar, coralliform, posterior nuclear, or polymorphic) of the opacification during lens development.

To date, 1460 novel and recurrent disease-causing sequence variants have been identified, with a well-defined distinct phenotype observed in 823.

Nevertheless, it is important to remember that phenotypic variability is seen within families with the same mutation.Different variants in different genes can present with the same phenotype.

Journal of Clinical and Experimental Ophthalmology is now accepting submissions on this topic. A standard EDITORIAL TRACKING SYSTEM is utilized for manuscript submission, review, editorial processing and tracking which can be securely accessed by the authors, reviewers and editors for monitoring and tracking the article processing. Manuscripts can be uploaded online at Editorial Tracking System (https://www.longdom.org/clinical-experimental-ophthalmology.html) or forwarded to the Editorial Office at manuscripts@longdom.org

Regards,

Lina Gilbert

Managing Editor

Pancreatic disorders and Therapy