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Volume 21, Number 22
15 November 2002

pp 5955-6287

Cover. The image shows protein inclusions (green label) that are formed within the nuclei (red label) of lens fibre cells in a group of murine inherited cataracts caused by similar gamma-crystallin mutations. The formation of these nuclear inclusions is one of the first steps along the pathway to cataract formation; these inclusions also disrupt nuclear function as an important intermediate step towards cataract. The mutations studied all lead to the truncation of domain 2 in the affected gamma-crystallins, causing the formation of these characteristic nuclear aggregates that have amyloid-like properties. A human inherited cataract with a very similar mutation to those presented in this study has recently been discovered. Studies by Sandilands et al. reveal some interesting parallels between this type of inherited cataract and Huntington's disease, a neurodegenerative disorder typified by amyloid-based nuclear inclusions. These studies demonstrate that cataracts too can be triggered by a toxic gain of function induced by certain crystallin mutations. For further details see Sandilands et al., pp. 6005--6014.

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