Inherited cataracts: Genetic mechanisms and pathways new and old

Cataract(s) is the clinical equivalent of lens opacity and is caused by light scattering either by high molecular weight protein aggregates in lens cells or disruption of the lens microarchitecture itself. Genetic mutations underlying inherited cataract can provide insight into the biological processes and pathways critical for lens homeostasis and transparency, classically including the lens crystallins, connexins, membrane proteins or components, and intermediate filament proteins. More recently, cataract genes have been expanded to include newly identified biological processes such as chaperone or protein degradation components, transcription or growth factors, channels active in the lens circulation, and collagen and extracellular matrix components. Cataracts can be classified by age, and in general congenital cataracts are caused by severe mutations resulting in major damage to lens proteins, while age related cataracts are associated with variants that merely destabilize proteins thereby increasing susceptibility to environmental insults over time. Thus there might be separate pathways to opacity for congenital and age-related cataracts whereby congenital cataracts induce the unfolded protein response (UPR) and apoptosis to destroy the lens microarchitecture, while in age related cataract high molecular weight (HMW) aggregates formed by denatured crystallins bound by alpha-crystallin result in light scattering without severe damage to the lens microarchitecture.

Automated summary

Cataracts are caused by protein aggregation or disruption of lens microarchitecture, and genetic mutations can provide insights into lens homeostasis. Congenital cataracts involve severe damage to lens proteins, while age-related cataracts are more susceptible to environmental insults, leading to different pathologies.