Transparency and non-refractive functions of crystallins--a proposal

Based on the premise that all crystallins have cellular and metabolically relevant catalytic activities, we propose that aberrant changes in non-crystallin (non-refractive) functions presage the appearance of cataractous pathologies in an otherwise highly stable edifice of transparency. This proposal is based on accumulating evidence from developmental, molecular and genetic studies that have established that crystallins are more than inanimate building blocks of the transparent lens fiber mass. The published work does not support the perceived dichotomy in the relevance of crystallin function (as essential) and non-crystallin function (as either of secondary importance or not essential at all), to the emergence and maintenance of the phenotype of transparency. A number of crystallin mutations have stage-specific phenotypes at developmental times when their concentrations have not reached 'crystallin' (high) proportions. There is heterogeneity in the cataract phenotypes associated with similar or identical mutations in different populations; the cataracts have disparate phenotypes even when the mutations are in the same gene. These data suggest that non-crystallin function is not merely a non-lens activity of a crystallin but an essential requirement within the lens itself.