Oxidative Stress and Inherited Cataracts in Mice

Graw, Jochen; Bors, Wolf; Michel, Christa; Reitmeir, Peter; Summer, Karl‐Heinz; Wulff, Andrea

doi:10.1159/000266931

Cited by 8 publications

(5 citation statements)

References 17 publications

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“…After birth, the lens capsule ruptures at the equatorial region, and synechiae with the iris occur (Graw, 1999). Biochemical examination of the cataractous Cat3 vao lenses demonstrated the presence of oxidative and osmotic stress (Graw et al, 1989;1990b). The dominant X-linked cataract mutation Xcat was recovered after parental radiation (Favor and Pretsch, 1990).…”

Section: Mutants Waiting For Molecular Characterizationmentioning

confidence: 99%

Congenital hereditary cataracts

Graw¹

2004

Int. J. Dev. Biol.

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126

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Congenital cataracts are rare and occur in developed countries with a frequency of 30 cases among 100,000 births with a further 10 cases being diagnosed during childhood. They reflect mainly genetically caused developmental alterations in the lens and surrounding ocular tissues. Even if modern Human Genetics has made large steps forward in the characterization of human hereditary disorders, the underlying developmental processes can only be investigated in model organisms. The mouse is such a good model because of its similarity (as a mammal) and its genetic characterization. This review brings together our genetic and developmental knowledge of congenital, human cataracts with the corresponding mouse models. First, early events will be influenced by genes coding for transcription factors like Pax6, Pitx3, Maf or Sox. If the lens is maturing, mutations affecting the lens membranes (aquaporins/Mip, Lim-2 or connexins) or the structural proteins of the cytosol of the lens fiber cells (the crystallins) become more important. From a genetic point of view it becomes obvious that cataract-causing mutations are not distributed randomly. The discovery of a broad variety of genes important for eye and lens development made much progress in the recent years. Nevertheless, there still remains a long list of mutations to be characterized and functionally investigated both in mouse and man indicating a broad genetic heterogeneity in that which clinicians simply refer to as a "cataract".

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Section: Mutants Waiting For Molecular Characterizationmentioning

confidence: 99%

Congenital hereditary cataracts

Graw¹

2004

Int. J. Dev. Biol.

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126

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“…The first morphological abnormality in the mutant lenses was observed as swelling of lens fibers at embryonic day 15.5 (Santhiya et al 1995). Biochemical investigations demonstrated an increase in the concentration of oxidized glutathione in the Crygb nop lenses over the wild type, which is not due to a corresponding decrease of an enzyme related to this metabolite (Graw et al , 1989a(Graw et al , 1990c. The nuclei of the cortical cells could also be detected in the area of the lens nucleus of the Crygb nop lenses (Graw et al 1990c).…”

Section: Differentiation Processes In the Developing Lensthe Crystallmentioning

confidence: 95%

“…Biochemical examination of the cataractous Cat3 Vao lenses demonstrated the presence of oxidative and osmotic stress (Graw et al 1989a(Graw et al , 1990b. It leads to a maldevelopment of the anterior lens epithelium and degeneration of the fibers.…”

Section: Cataracts: Inherited Anomalies Of the Lensmentioning

confidence: 99%

Vertebrate Eye Development

Fini¹

2000

Results and Problems in Cell Differentiation

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“…The 2.5-to 5-fold increase in the concentration of oxidized glutathione (GSSG) in the Crygb nop and Cryge t lenses over the wild type could not be explained by a corresponding decrease in the enzymes reverting this metabolite to its reduced stage (Graw et al, 1984(Graw et al, , 1989a(Graw et al, , 1990a.…”

Section: Connexins In Eye Developmentmentioning

confidence: 98%

Developmental genetics in ophthalmology

Graw

Löster

2003

Ophthalmic Genetics

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Much of our knowledge about the function of genes in mammalian development has been derived from the molecular analysis of spontaneous or induced mutations in the mouse. Since mutations affecting the mouse eye can be easily identified, a remarkable number of mutant lines provide animal models for congenital anomalies in man. To understand the mechanisms of lens development in detail, the isolation of the corresponding genes and the characterization of the mutations at the molecular level are important. A prerequisite for molecular analysis is the chromosomal localization of the gene. In this review, some mutants from our institute will be discussed according to the embryological time scale of the expression of the affected genes, reflecting also their genetic hierarchy. (1) In the aphakia mouse mutant, two deletions in the promoter of the homeobox transcription factor Pitx3 lead to a loss of its function and to an arrest of eye development at the lens stalk stage. Mutations in the homologous human PITX3 gene have been demonstrated to be causative of cataracts and the dysmorphology of the anterior segment of the eye. (2) Connexin50 is present in the lens vesicle. Later on, it becomes abundant in the anterior part of the fiber cells and in the lens epithelial cells. Mutations in the connexin50-encoding gene Gja8 lead to dominant cataracts. (3) alphaA-crystallin is present in the mouse lens cup, in the posterior half of the lens vesicle, and later in a high concentration in the lens fiber cells. Mutations in the alphaA-crystallin-encoding gene Cryaa lead to recessive and dominant cataracts. (4) Mutations in the gamma-crystallin -encoding genes (Cryg) are the most frequent cause of congenital, dominant nuclear, or total cataracts in the mouse. Indications from our first studies in congenital human cataracts support these data. (5) Some postnatal, progressive cataracts have been characterized by mutations in the beta-crystallin -encoding genes (Cryb). Since at least one of them is also expressed in the retina and the brain, effects on these tissues have to be considered, too.

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Oxidative Stress and Inherited Cataracts in Mice

Cited by 8 publications

References 17 publications

Congenital hereditary cataracts

Congenital hereditary cataracts

Vertebrate Eye Development

Developmental genetics in ophthalmology

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