On the nature of hereditary cataract in strain 13/N guinea pigs

Abstract

PURPOSE. Congenital nuclear cataracts in strain 13/N guinea pigs are caused by a single splice-site mutation in the zeta-crystallin gene. Very little is known of the physical factors involved in lens opacification of this system. The aim of this study is to elucidate the biophysical processes causing the nuclear turbidity. METHODS. Normal, homozygous and heterozygous mutant guinea pig lenses were studied. Polarized light scattering measurements were performed on thin sections of lenses as a function of scattering angle. Scattering intensities were collected in two modes, I" and I+. The total water content of lenses was determined by thermogravimetric analysis. The nonfreezable (bound) water content was obtained by differential scanning calorimetry. The morphology of lenses was investigated by scanning electron microscopy. RESULTS. Normal lenses scatter 5- to 10-fold less light than cataractous lenses at wide angles in both modes. The intensity ratios of the two modes imply that most of the scattering comes from density fluctuations; 10–20% of the turbidity may be contributed by orientation fluctuations. The nucleus of heterozygous cataractous lenses contain less total water than normal lenses, whereas the cortex has the same hydration as the normal lens. The nonfreezable water content of the cataractous nucleus is higher than that of the normal lens. Scanning electron microscopy showed frequent truncation of the fiber cells, cavitations and occasional longitudinal splitting resulting in hollow cylinder formation in the nucleus of the cataractous lens. CONCLUSION. Mutation of zeta-crystallin in guinea pigs causes a congenital cataract. A number of supramolecular events contribute to the turbidity. The mobile water leaves the nuclear fiber cells, causing a collapse of supramolecular structures. Both the size of the aggregates and their refractive index increase by this dehydration process, contributing to the turbidity. The truncation and hollowing of fiber cells causes the orientation fluctuations that also increase turbidity.