Conformational and Thermodynamic Features of Meibum in Adolescents and Adults with Graft‐versus‐host Disease

Abstract

PurposeGraft‐versus‐host disease (GvHD) is a common complication of allogenic hematological stem cell transplantations that is often associated with dry eye disease (DED) classified as a mixture of meibomian gland dysfunction and aqueous tear deficiency. The temperature‐dependence of conformational changes in human meibum (hM) was measured in a comparative study to elucidate the potential impact of GvHD on hM composition, structure and function with DED.MethodsDonors received full ophthalmic eye exams and DED was clinically diagnosed. A total of 28 donors without DED were separated into two pools: adolescent (age: 17 ± 1 and 63% male) and adult (age: 42 ± 4 and 73% male). Adolescent (age: 15 ± 1 and 80% male) and adult (age: 45 ± 5 and 30% male) pools from a total of 15 donors affected by both DED and GvHD were also tested. The extracted hM was placed in d‐chloroform and analyzed by Fourier Transform Infrared Spectroscopy (FTIR).ResultsAmong the measured parameters, the lipid order (% trans) in hM at 36°C increased significantly from adolescents without DED (35.3 ± 4%) to those affected by GvHD (54.7 ± 4%). A similar trend (33.3 ± 0.09% without DED to 38.0 ± 4% with DED/GvHD) was observed in hM from adults. The change in enthalpy for the order‐to‐disorder transition decreased significantly with DED/GvHD in both adolescents (from 163 ± 10 Kcal/mol without DED to 134 ± 9 Kcal/mol with DED/GvHD) and adults (141 ± 5 Kcal/mol without DED to 126 ± 11 Kcal/mol with DED/GvHD). The phase transition temperature (C°) was significantly higher in adolescents with DED/GvHD (38 ± 1°C) compared to donors without DED (30.4 ± 0.6°C), but the increase was less pronounced in adults with DED/GvHD (31 ± 1°C) relative to those without DED (30.0 ± 0.4°C).ConclusionBoth age and DED lead to conformational and thermodynamic differences in hM. Increases in lipid order and transition temperatures were observed in hM with GvHD. However, these relative increases were more pronounced in hM from adolescents than from adults. The decrease of change in enthalpy for adolescents was more pronounced compared with adults. The conformational and thermodynamic differences observed with age and, importantly, with DED/GvHD are indicative of compositional changes in hM that could impact tear film stability.Support or Funding InformationMajor support was obtained from the National Institute of Health (NIH) EYO RO126180 (DB); NIH Research Supplements to Promote Diversity in Health‐Related Research EYO RO126180S‐1 (SS); and an unrestricted grant from Research to Prevent Blindness, Inc. New York, NY, USA.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.