Clinical and experimental advances in congenital and paediatric cataracts

Abstract

Cataracts (opacities of the lens) are frequent in the elderly, but rare in paediatric practice. Congenital cataracts (in industrialized countries) are mainly caused by mutations affecting lens development. Much of our knowledge about the underlying mechanisms of cataractogenesis has come from the genetic analysis of affected families: there are contributions from genes coding for transcription factors (such as FoxE3, Maf, Pitx3) and structural proteins such as crystallins or connexins. In addition, there are contributions from enzymes affecting sugar pathways (particularly the galactose pathway) and from a quite unexpected area: axon guidance molecules like ephrins and their receptors. Cataractous mouse lenses can be identified easily by visual inspection, and a remarkable number of mutant lines have now been characterized. Generally, most of the mouse mutants show a similar phenotype to their human counterparts; however, there are some remarkable differences. It should be noted that many mutations affect genes that are expressed not only in the lens, but also in tissues and organs outside the eye. There is increasing evidence for pleiotropic effects of these genes, and increasing consideration that cataracts may act as early and readily detectable biomarkers for a number of systemic syndromes.

The ocular lens: a classic model for development, physiology and disease

“…Amanda Churchill and Jochen Graw highlight clinical and experimental advances in congenital and paediatric cataracts in their article [6]. These authors cover the genetic analysis of families with vision defects, including discussion of various mutations in genes coding for transcription factors, for example FoxE3, Maf and Pitx3, structural proteins such as crystallins and connexins, metabolic pathways including enzymes involved in sugar metabolism, such as galactose, and, intriguingly, axon guidance molecules.…”

A novel missense mutation in HSF4 causes autosomal-dominant congenital lamellar cataract in a British family

“…Congenital cataract can occur in isolation or in association with other non-ocular manifestations, and is a predominant feature in more than 200 genetic disorders. Congenital cataract may be familial and display considerable genotypic and phenotypic heterogeneity 4 .…”

An Epha4/Sipa1l3/Wnt pathway regulates eye development and lens maturation

“…The most common cause of blindness worldwide is a congenital or acquired cataract characterized by non-transparent opaque lenses (Churchill and Graw, 2011). On a molecular and cellular level, a congenital cataract can be caused by the loss of expression of lensspecific proteins such as crystallins, the presence of light-scattering organelles (i.e.…”