Lipid conformational order and the etiology of cataract and dry eye

Abstract

Lens and tear film lipids are as unique as the systems they reside in. The major lipid of the human lens is dihydrosphingomylein, found in quantity only in the lens. The lens contains a cholesterol to phospholipid molar ratio as high as 10:1, more than anywhere in the body. Lens lipids contribute to maintaining lens clarity, and alterations in lens lipid composition due to age are likely to contribute to cataract. Lens lipid composition reflects adaptations to the unique characteristics of the lens: no turnover of lens lipids or proteins; the lowest amount of oxygen than any other tissue and contains almost no intracellular organelles. The tear film lipid layer (TFLL) is also unique. The TFLL is a thin, 100 nm layer of lipid on the surface of tears covering the cornea that contributes to tear film stability. The major lipids of the TFLL are wax esters and cholesterol esters that are not found in the lens. The hydrocarbon chains associated with the esters are longer than those found anywhere in the body, as long as 32 carbons, and many are branched. Changes in the composition and structure of the 30,000 different moieties of TFLL contribute to the instability of tears. The focus of the current review is how spectroscopy has been used to elucidate the relationships between lipid composition, conformational order and function and the etiology of cataract and dry eye.

Meibum lipid hydrocarbon chain branching and rheology after hematopoietic stem cell transplantation

“…The correlation between meibum stiffness and tear film stability was highlighted in the Introduction and recently reviewed [ 10 ]. Too much lipid order may keep meibum from flowing out of the meibomian glands.…”

“…Using the same reasoning for age above, it is reasonable that the PT lipids would form stiffer, thicker, viscous and patchy heterogeneous films on the tear film surface which could lower tear film stability and impede their spreading between blinks [ 6 ]. Tear film stability, and TFLL structural order varies greatly from person to person, however, correlations and trends between the stability and structural order values could be made between large cohorts [ 10 ]. From other age related studies of meibum from normal donors and meibum from donors with dry eye from Meibomian gland dysfunction and Parkonson's disease, the current study of donors with HSCT supports the idea that a more ordered lipid could contribute to or be a marker of dry eye [ 10 ].…”

“…Tear film stability, and TFLL structural order varies greatly from person to person, however, correlations and trends between the stability and structural order values could be made between large cohorts [ 10 ]. From other age related studies of meibum from normal donors and meibum from donors with dry eye from Meibomian gland dysfunction and Parkonson's disease, the current study of donors with HSCT supports the idea that a more ordered lipid could contribute to or be a marker of dry eye [ 10 ]. Thus, the presence of more ordered lipids with higher (C s −1 ) max values and longer pressure-area isotherm transitions, as observed for PT lipids, are indicators of less stable lipid films at the air-tear interface [ 10 , 28 ].…”

“…Approximately 80% of the lipid in tears originates from the meibomian glands located in the eye lids [ [7] , [8] , [9] ]. The relationships between meibum lipid structural order (stiffness) measured spectroscopically, to tear film stability has been reviewed [ 10 ]. Tear film stability can be inferred from tear breakup time and blink rates measurements.…”

“…Too much lipid order may keep meibum from flowing out of the meibomian glands. Correlations between Meibum lipid order and tear film stability have been made with age between 0 and 25 years old, meibomian gland dysfunction, with donors who have had hematopoietic stem cell transplantation (HSCT) and donors with Parkinsons's disease [ 10 ]. Correlation does not necessitate cause, but the relationship between hydrocarbon chain order and tear film stability is intriguing.…”