PubMed Health⌕ Search

Biomedical subjects

John M Tiffany

Publications and source records attributed to John M Tiffany.

11 recordsLinked to original sources

Human tear viscosity: an interactive role for proteins and lipids.

Human tear viscosity is poorly understood. Tears need to remain on the ocular surface for lubrication without causing damage to the surface epithelia due to drag when blinking. Whole tears are shear-thinning (non-Newtonian), which cannot be explained by the amount of mucin present, nor by individual proteins. Whole tears minus lipids become Newtonian. Though no free lipids had previously been found in collected tears, tear lipocalin (TL), a major tear protein, is known to bind lipids. In this study, we aimed to confirm whether there are any free lipids in collected tears, and to clarify the combined contribution of tear proteins to viscosity, including experiments on recombinant TL, both without (apo-TL) and with (holo-TL) bound lipid. We also investigated possible oligomer formation by holo- and apo-TL as a mechanism for viscosity using SDS-PAGE and analytical ultracentrifugation (AU). For comparison, we have included results for beta-lactoglobulin, a well-characterised lipocalin protein. No free lipids were detected in whole tears. Rheology showed that any protein combination that included lysozyme or lactoferrin was shear-thinning, as was apo-TL, though holo-TL was Newtonian (linear). Results from SDS-PAGE and AU showed apo-TL to be entirely monomeric, but holo-TL showed some dimerization. Both apo- and holo-beta-lactoglobulin exhibited a monomer-dimer equilibrium. We conclude that hetero-protein interactions, possibly electrostatic, involving lipid-binding-induced structural changes to TL, significantly contribute to the viscosity of human tears.

Carrier Proteins↗

Relationship between tear volume and tear meniscus curvature.

OBJECTIVE: To investigate the relationship between tear volume and tear meniscus curvature by means of the video meniscometer. METHODS: Eleven eyes of 11 patients with severe dry eye were studied (all female; mean +/- SD age, 66.2 +/- 7.7 years; 7 left eyes and 4 right eyes), each of whose puncta had been therapeutically occluded. Four instillations of balanced salt solution were given at intervals of 1 minute in each studied eye, with the concentration increasing in 5-microL steps from 5 to 20 microL. Before and after the instillation of balanced salt solution, tear meniscus changes were recorded by video meniscometer and radius of the meniscus was calculated from the printed images by means of the concave mirror formula. RESULTS: The mean radius of the meniscus increased linearly with increased drop volume (r(2) = 0.65, P<.001), with mean +/- SD radius values of 0.24 +/- 0.08 mm at baseline and 0.48 +/- 0.13, 0.62 +/- 0.13, 0.84 +/- 0.26, and 1.00 +/- 0.32 mm after separate instillations of 5, 10, 15, and 20 microL of balanced salt solution, respectively. For each subject, a significantly different slope defining the relationship between instilled volume and meniscus radius was seen (0.016-0.063 mm/ microL; mean +/- SD, 0.039 +/- 0.015 mm/ microL), which was thought to depend on the difference in capacity of the fluid reservoir over the ocular surface. CONCLUSIONS: This study confirmed that the volume of instilled eyedrops is linearly related to the resulting radius of the tear meniscus, suggesting that this radius is a useful measure in monitoring the tear volume. This is likely to have implications both for dry eye diagnosis and for confirming the efficacy of punctal occlusion in this condition.

Aged↗

The influence of eyelid temperature on the delivery of meibomian oil.

The aim of this study is to establish the effect of heating and cooling of the eyelid on the delivery of oil from the meibomian glands, as indicated by the extent of re-establishment of the reservoir of meibomian oil on the human eyelid margin, resulting from 10 conscious blinks, following pre-cleaning by a hexane swab. A standard handling sequence was followed. Step 1. Both upper and lower eyelids of both eyes of human volunteers were cleaned by a hexane swab and measured by a Meibometer to show satisfactory removal of the pre-existing oil (initial reading less than 60 instrumental units (IU)). The volunteers were then asked to blink 10 times at their normal rate. Then the eyelid was re-measured by the Meibometer. Step 2. The closed eyelids were heated for 5 min by a 250 W infrared lamp from a distance of 50 cm. The eyelid temperature was measured by an infrared thermometer, then Step 1 was repeated. Step 3. The eyelids were cooled for 5 min by an ice-pack (crushed ice in a towel). The eyelid temperature was measured, then Step 1 was repeated. Both eyes of 20 female subjects, aged 68 +/- 3 S.E.M. (range 52-84) years were examined. The mean instrumental reading (IU +/- S.E.M.) after 10 blinks at 33.4 +/- 0.1 degrees C was 154 +/- 12. On increasing the eyelid surface temperature by 4.9 +/- 0.3 degrees C we obtained an increase of 49 +/- 9 IU. On decreasing it by 7.6 +/- 0.4 degrees C we obtained a decrease of 46 +/- 9 IU. We conclude that temperature significantly influences the delivery of the meibomian gland secretion. Our results are in agreement with the 10-blink recovery value of 191 +/- 9.3 IU previously reported. They also agree with the reported benefit of warm compresses to improve delivery from dysfunctional glands. The most likely explanation for our findings is a change in the viscosity of the meibomian oil.

Aged↗

Retention of reversibly thermo-gelling timolol on the human ocular surface studied by video meniscometry.

PURPOSE: To investigate the retention of reversibly thermo-gelling timolol (TG-timolol) on the human ocular surface using video meniscometry. METHODS: The study population consisted of 14 healthy volunteers with no external eye disease. Fifteen microl TG-timolol were instilled into one eye of each subject and the same volume of aqueous, timolol ophthalmic solution was instilled in the fellow eye, in a masked fashion. Tear meniscus curvature was monitored at the center of the lower meniscus in each eye, using a newly-developed video meniscometer, before and at one-minute intervals for ten minutes after, the instillation. The radius of meniscus curvature (R) was calculated from printed video-images using the concave mirror formula. The change in R with time after instillation was compared for the two groups. RESULTS: The change in meniscus radius with time t [defined as deltaR(t) = R(t) - R(0)] showed a significant exponential regression in both the TG-timolol and the timolol groups. There was a significant difference in the value of deltaR(5) and deltaR(10) between eyes with TG-timolol [deltaR(5) = 0.29 mm, deltaR(10) = 0.18mm] and eyes with timolol only [deltaR(5) = 0.10mm, deltaR(10) = 0.06 mm] [deltaR(5): P < 0.001, deltaR(10): P < 0.001]. The area under each regression curve of deltaR(t), an indicator of vehicle retention, was greater in the eyes treated with TG-timolol than in those receiving timolol only (2.09 vs. 0.56, P < 0.001). CONCLUSIONS: The present study demonstrated that the reversibly thermo-gelling timolol was better retained at the ocular surface than conventional, aqueous timolol.

Antihypertensive Agents↗

Dynamic changes in tear meniscus curvature at the rigid contact lens edge.

PURPOSE: To investigate dynamic changes in tear meniscus curvature at the edge of a rigid contact lens. METHODS: Four eyes of four men and seven eyes of seven women who were daily wearers of rigid contact lenses were enrolled in the study. A digital video-meniscometer was used to observe real-time changes in tear meniscus curvature. Quantitative measurements have not previously been made at these locations. RESULTS: The meniscus at the lens edge showed stereotypical changes with each blink. The meniscus radius is lowest at the end of the up-phase of the blink and then increases to a steady value 0.213 +/- 0.024 mm (mean +/- SD, n = 6) after about 1 second. CONCLUSIONS: The video-meniscometer permitted observation of real-time changes in meniscus curvature at the contact lens edge during the blink. The short radius at the end of the up-phase suggests that tears are drawn away from the lens during the upward movement of the lid and lens. The restoration of a longer radius of curvature in the period that follows is thought to be due to a flow of fluid into the meniscus from the neighboring tear film.

Adult↗

Viscosity of alpha-crystallin solutions.

Accommodation in the mammalian lens requires flexure of lens fibres and some redistribution of their contents involving limited viscous flow. Shear-dependent viscosity of bovine alpha-crystallin solutions was determined with the Contraves Low-Shear Rheometer between 4.4 and 347 mg ml(-1), and at 15.5, 25, 30, and 37 degrees C. All solutions showed significant shear thinning, with markedly higher viscosity at physiological levels of approximately 300 mg ml(-1). Viscosity-concentration graphs were similar at low (1.0 s(-1)) and high (94.5 s(-1)) shear rates, indicating low molecular interaction in solution. Arrhenius plots which might have indicated the size of the energy barrier to displacement of molecules or aggregates were inconclusive.

Animals↗

The thickness of the tear film.

Measurements of the thickness of the pre-corneal tear film, pre-lens tear film, post-lens tear film, and the lipid layer on the surface of the tear film are summarized. Spatial and temporal variations in tear film thickness are described. Theoretical predictions of tear film thickness are discussed. Mechanisms involved in the upward drift of the tear film after a blink, and in the formation of dry spots, are considered.

Animals↗