No turnover in lens lipids for the entire human lifespan

Abstract

Lipids are critical to cellular function and it is generally accepted that lipid turnover is rapid and dysregulation in turnover results in disease (Dawidowicz 1987; Phillips et al., 2009; Liu et al., 2013). In this study, we present an intriguing counter-example by demonstrating that in the center of the human ocular lens, there is no lipid turnover in fiber cells during the entire human lifespan. This discovery, combined with prior demonstration of pronounced changes in the lens lipid composition over a lifetime (Hughes et al., 2012), suggests that some lipid classes break down in the body over several decades, whereas others are stable. Such substantial changes in lens cell membranes may play a role in the genesis of age-related eye disorders. Whether long-lived lipids are present in other tissues is not yet known, but this may prove to be important in understanding the development of age-related diseases.DOI: http://dx.doi.org/10.7554/eLife.06003.001

Distribution of Glycerophospholipids in the Adult Human Lens

“…Overall, the annular distribution of intact glycerophospholipids revealed here by MALDI imaging are consistent with greater susceptibility of these molecules to oxidative and hydrolytic degradation over time, in contrast with more robust sphingolipids [22]. As there is no lipid turnover in the inner parts of the lens to replenish degraded GPLs [3], a diminishing concentration from the outer to the core is expected with age and validated by our observations [12]. Overall the decrease in GPL will result in a concomitant increase in the ratio of sphingolipids to GPLs, which may decrease diffusion through the tissue and protect against further oxidation and degradation [22].…”

“…The lens is an ocular tissue that grows throughout the life span of an organism with newly differentiated fibre cells laid down upon older cells that are present from birth [1]. There is no protein [2] or lipid [3] turnover in the lens, thus structural and enzymatic proteins and lipids that are present at birth remain for the lifetime of the individual. In addition, upon fibre cell differentiation, all intracellular organelles are degraded [4].…”

Synchrotron-based FTIR microspectroscopy of protein aggregation and lipids peroxidation changes in human cataractous lens epithelial cells

“…Besides, lens lipid composition alters importantly in cataract 11 . These changes could lead to crystalline structure of the lens, disturbed with age, the oxidative damage accumulates in the lens, which decrease turnover of lipids or proteins in the lens 12,13 . Nucleic acids are also prone to these changes, as oxidative stress and changed antioxidative defense capacity also modify the rate of telomere shortening 14 .…”

Why Is Very High Cholesterol Content Beneficial for the Eye Lens but Negative for Other Organs?

“…In this respect, the lens fiber cell membranes are unique. There is no turnover in the center of the human ocular lens [46] and, as such, oxidation damage accumulates with age. The eye lens adapts to these age-related changes through the lipid modification of fiber cell membranes.…”