Increased molar ratio of free fatty acids to albumin in blood as cause and early biomarker for the development of cataracts and Alzheimer's disease.

Cataracts and Alzheimer's disease (AD) are closely linked and are associated with aging and with systemic diseases that increase the molar ratio of free fatty acids to albumin (mFAR) in the blood. From the results of our earlier studies on the development of senile cataracts and from results recently published in the literature on the pathogenesis of Alzheimer's disease, we suggest that there is a common lipotoxic cascade for both diseases, explaining the strong connection between aging, an elevated mFAR in the blood, cataract formation, and AD. Long-chain free fatty acids (FFA) are transported in the blood as FFA/albumin complexes.

Fatty acid cytotoxicity to human lens epithelial cells.

Data obtained with the neutral red cytotoxicity assay reveal that human lens epithelial cells in culture are highly sensitive to low micromolar concentrations of unsaturated, cis-configured fatty acids in the following order: arachidonic acid>linolenic acid=linoleic acid=oleic acid, whereas the saturated fatty acids are much less effective. Though the cytotoxic effects of the unsaturated fatty acids could not be discerned from effects of their oxidation products, the fact that oleic acid is equally cytotoxic as linoleic acid or linolenic acid as well as previously reported findings with bovine lens epithelial cells support the idea that the unsaturated fatty acid molecules directly account for the cytotoxicity and not their products of lipid peroxidation. Bleb formation and cell retraction are early morphological signs of fatty acid-induced lens cell damage.

Serum withdrawal induces a redistribution of intracellular gelsolin towards F-actin in NIH 3T3 fibroblasts preceding apoptotic cell death.

The intracellular distribution of gelsolin in NIH 3T3 cells was examined by immunostaining using affinity-purified polyclonal gelsolin antibodies before and after induction of apoptosis by serum withdrawal. Serum deprivation induced detachment of an increasing number of NIH 3T3 cells, but also apoptosis in attached cells as verified morphologically by chromatin condensation, nuclear fragmentation and labelling of their periphery by FITC-annexin V. Ongoing apoptosis was also demonstrated by activation of caspase-3 activity and chromatin cleavage into high-molecular-mass fragments, although no internucleosomal chromatin degradation (DNA-ladder formation) was detected.

[Human cultured lens cells. II. Characterization of established lens cell lines and test of their suitability for cytotoxicity tests].

Background: Human lens cells in culture may be valuable tools to discover cataractogenic risk factors. Here we report on the characterization of established human lens cells and their use in cytotoxicity tests.

Material And Methods: Adhesion dependence was tested by an autoradiographic method.

[Human lens cells in culture. I. Isolation of adult lens epithelial cells from lens capsule preparations and reactivation of nucleus-containing fiber cells].

Background: Bovine lens epithelial cells in culture revealed a high sensitivity against micromolar concentrations of linoleic acid. To prove the assumption that unsaturated free fatty acids are risk factors for cataractogenesis, human lens cell lines are needed. Furthermore, the reactivation of nucleus-containing fiber cells to mitotic growth may hint at their role in after cataract genesis.