Lipids and the ocular lens

Borchman, Douglas; Yappert, Marta C.

doi:10.1194/jlr.r004119

Cited by 139 publications

(142 citation statements)

References 199 publications

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“…Phospholipids constitute approximately 60% of human lens membranes and play the main role in its transparency [9]. The lipid contents especial dihydrosphingomyelin the main lens membrane component undergo dramatic alterations with age and cataractogenesis [31].…”

Section: Discussionmentioning

confidence: 99%

Biochemical and Molecular Markers of Congenital and Senile Cataractous Lenses

El‐Sayyad¹,

Ym²,

Khalifa³

et al. 2017

J Mol Biomark Diagn

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Section: Discussionmentioning

confidence: 99%

Biochemical and Molecular Markers of Congenital and Senile Cataractous Lenses

El‐Sayyad¹,

Ym²,

Khalifa³

et al. 2017

J Mol Biomark Diagn

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“…6 point to an increase in DHSM (d18:0/16:0) in the barrier region with age, there is insuffi cient data (a total of only two young and and also in the lens cortex and nucleus separately ( 28 ). Indeed, these and other changes in the ocular lens lipidome have been the subject of a recent comprehensive review ( 29 ). There are, however, no existing data describing the relationship between age and glycerophospholipids in the barrier region.…”

Section: Changes In Sphingomyelin Content Of the Barrier Region With Agementioning

confidence: 99%

Sphingolipid distribution changes with age in the human lens

Deeley

Hankin

Friedrich

et al. 2010

Journal of Lipid Research

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characterizing these can have clinical relevance for understanding the molecular basis of ocular conditions such as presbyopia ( 2 ) and nuclear cataract ( 3, 4 ).It is not known which are the critical factors predisposing the human lens to age-related nuclear (ARN) cataract. Research from one of us, over many years, suggests that the formation of an internal barrier to the diffusion of small molecules may be a key event in the onset of this pathology ( 5, 6 ). The barrier forms in the normal lens at middle age and uncouples the center of the lens from the metabolically active outer region. Because the lens grows continuously throughout life, the outmost part of the lens is the region that was formed most recently and has the highest concentration of active enzymes ( 7,8 ). It is where the major antioxidant glutathione (GSH) is synthesized and the oxidized form of glutathione rereduced ( 9, 10 ). Since GSH is essential for maintaining a reducing environment in the lens center and for protection of protein structure, formation of the barrier allows oxidative modifi cation of nuclear proteins that is the hallmark of nuclear cataract. The dimensions of the barrier region (7 mm equatorial × 3 mm axial) corresponds to the part of the adult lens that was synthesized immediately after birth ( 11,12 ).Recent data implicate the binding of denatured proteins to the fi ber cell membrane as the mechanism responsible for the barrier ( 13 ), possibly by occluding the membrane pores that normally facilitate the movement of GSH and water from cell to cell via connexon ( 14 ) and aquaporin 0 ( 15 ) channels, respectively. Moreover, aquaporin 0 requires interaction with distinct membrane lipids to form its correct functional conformation ( 15 ). If interactions with fi ber cell Abstract The formation of an internal barrier to the diffusion of small molecules in the lens during middle age is hypothesized to be a key event in the development of age-related nuclear (ARN) cataract. Changes in membrane lipids with age may be responsible. In this study, we investigated the effect of age on the distribution of sphingomyelins, the most abundant lens phospholipids. Human lens Due to a lack of turnover ( 1 ), the lens is an ideal tissue for examining age-related changes to biomolecules, and

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“…As a consequence, acyl transfer from the membrane to AQP0 would be expected produce a distribution of acyl groups that reflects the acyl composition of PE and PS, and to a lesser extent (due to their low abundance), PI lipids. The major lipid classes of bovine lens membranes are, in decreasing order of abundance, PC ≈ PE ≈ SM > PS > PI (when PE plasmalogens are included in the PE fraction) [20,21]. Cholesterol is also a major component [22,23].…”

Section: Discussionmentioning

confidence: 99%

“…Human lens membranes are significantly more enriched in cholesterol and sphingolipids than bovine lens membranes [20,21]. Within the sphingolipids, there is a pronounced shift to longer and more saturated alkyl chains [27], which is reflected in the fatty acid distribution for the membrane as a whole [28].…”

Section: Discussionmentioning

confidence: 99%

The lipidation profile of aquaporin-0 correlates with the acyl composition of phosphoethanolamine lipids in lens membranes

Ismail¹,

Mosely²,

Tapodi³

et al. 2016

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT AbstractThe lens fiber major intrinsic protein (otherwise known as aquaporin-0 (AQP0), MIP26 and MP26) has been examined by mass spectrometry (MS) in order to determine the speciation of acyl modifications to the side chains of lysine residues and the N-terminal amino group. The speciation of acyl modifications to the side chain of one specific, highly conserved lysine residue (K238) and the N-terminal amino group of human and bovine AQP0 revealed, in decreasing order of abundance, oleoyl, palmitoyl, stearoyl, eicosenoyl, dihomo--linolenoyl, palmitoleoyl and eicosadienoyl modifications. In the case of human AQP0, an arachidonoyl modification was also found at the N-terminus. The relative abundances of these modifications mirror the fatty acid composition of lens phosphatidylethanolamine lipids. This lipid class would be expected to be concentrated in the inner leaflet of the lens fiber membrane to which each of the potential AQP0 lipidation sites is proximal. Our data evidence a broad lipidation profile that is both species and site independent, suggesting a chemical-based ester aminolysis mechanism to explain such modifications.

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Lipids and the ocular lens

Cited by 139 publications

References 199 publications

Biochemical and Molecular Markers of Congenital and Senile Cataractous Lenses

Biochemical and Molecular Markers of Congenital and Senile Cataractous Lenses

Sphingolipid distribution changes with age in the human lens

The lipidation profile of aquaporin-0 correlates with the acyl composition of phosphoethanolamine lipids in lens membranes

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