Animal model systems of senile cataract and lens crystallin stability are essential to understand the complex nature of lens transparency. Our aim in this study was to assess the long-lived Antarctic toothfish Dissostichus mawsoni (Norman) as a model system to understand long-term lens clarity in terms of solubility changes that occur to crystallins. We compared the toothfish with the mammalian model cow lens, dissecting each species' lens into a cortex and nuclear region. In addition to crystallin distribution, we also assayed fatty acid (FA) composition by negative ion electrospray ionization mass spectrometry (ESI-MS). The majority of toothfish lens crystallins from cortex (90.4%) were soluble, whereas only a third (31.8%) from the nucleus was soluble. Crystallin solubility analysis by SDS-PAGE and immunoblots revealed that relative proportions of crystallins in both soluble and urea-soluble fractions were similar within each species examined and in agreement with previous reports for bovine lens. From our data, we found that both toothfish and cow crystallins follow patterns of insolubility that mirror each animals lens composition with more γ crystallin aggregation seen in the toothfish lens nucleus than in cow. Toothfish lens lipids had a large amount of polyunsaturated fatty acids that were absent in cow resulting in an unsaturation index (I(U)) four-fold higher than that of cow. We identified a novel FA with a molecular mass of 267 mass units in the lens epithelial layer of the toothfish that accounted for well over 50% of the FA abundance. The unidentified lipid in the toothfish lens epithelia corresponds to either an odd-chain (17 carbons) FA or a furanoid. We conclude that long-lived fishes are likely good animal models of lens crystallin solubility and may model post-translational modifications and solubility changes better than short-lived animal models.