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Biomedical subjects

J Sebag

Publications and source records attributed to J Sebag.

At least 19 recordsLinked to original sources

Imaging vitreous.

Purpose Imaging vitreous is a quest to view what is, by design, invisible. This treatise will review significant historical aspects, past and present imaging methodologies, and imaging techniques that are currently in development for future research and clinical applications. Methods Classic and modern histologic techniques, dark-field slit microscopy, clinical slit lamp biomicroscopy, standard and scanning laser ophthalmoscopy, ultrasonography, optical coherence tomography, magnetic resonance and raman spectroscopy, and dynamic light scattering methodologies are presented. Results The best available histologic techniques for imaging vitreous are those that avoid rapid dehydration of vitreous specimens. Dark-field slit microscopy enables in vitro imaging without dehydration or tissue fixatives. Optical coherence tomography enables better in vivo visualization of the vitreo-retinal interface than scanning laser ophthalmoscopy and ultrasonography but does not image the vitreous body. Dynamic light scattering can determine the average sizes of vitreous macromolecules within the vitreous body as well as possibly image the posterior vitreous cortex once detached, while Raman spectroscopy can detect altered vitreous molecules, such as glycated collagen and other proteins in diabetic vitreopathy. Conclusions The inability to adequately image vitreous hinders a more complete understanding of its normal structure and how this changes in aging and disease. The combined use of more than one technique could provide better imaging of vitreous for future investigational and clinical purposes.

Age Factors↗

Quantitative molecular characterization of bovine vitreous and lens with non-invasive dynamic light scattering.

The non-invasive technique of dynamic light scattering (DLS) was used to quantitatively characterize vitreous and lens structure on a molecular level by measuring the sizes of the predominant particles and mapping the three-dimensional topographic distribution of these structural macromolecules in three spatial dimensions. The results of DLS measurements in five fresh adult bovine eyes were compared to DLS measurements in model solutions of hyaluronan (HA) and collagen (Coll). In the bovine eyes DLS measurements were obtained from excised samples of gel and liquid vitreous and compared to the model solutions. Measurements in whole vitreous were obtained at multiple points posterior to the lens to generate a three-dimensional 'map' of molecular structure. The macromolecule distribution in bovine lens was similarly characterized.In each bovine vitreous (Bo Vit) specimen, DLS predominantly detected two distinct particles, which differed in diffusion properties and hence size. Comparisons with model vitreous solutions demonstrated that these most likely corresponded to the Coll and HA components of vitreous. Three-dimensional mapping of Bo Vit found heterogeneity throughout the vitreous body, with different particle size distributions for Coll and HA at different loci. In contrast, the three-dimensional distribution of lens macromolecules was more homogeneous. Thus, the non-invasive DLS technique can quantitate the average sizes of vitreous and lens macromolecules and map their three-dimensional distribution. This method to assess quantitatively the macromolecular structure of vitreous and lens should be useful for clinical as well as experimental applications in health and disease.

Animals↗

Shaken not stirred.

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Clinical Trials as Topic↗

Neuron specific enolase in retinal detachment.

PURPOSE: Neuron Specific Enolase (NSE) is released following central nervous system (CNS) distress. As retina is part of the CNS, NSE levels were measured in the subretinal fluid (SRF), aqueous, and serum of patients with primary rhegmatogenous retinal detachment (RD). METHODS: Radioimmunoassay was used to determine NSE levels in the SRF, aqueous, and serum of 13 patients (28-92 years old, mean = 71 years) with RD. As controls, NSE was measured in the aqueous of 6 patients undergoing cataract surgery and in serum of 18 patients without ophthalmological or neurological diseases. RESULTS: SRF levels of NSE ranged from 50-200 microg/l (mean +/- s.d. = 150 +/- 57). NSE levels in aqueous from patients with RD were 2-140 microg/l (mean +/- s.d. = 39 +/- 42), significantly higher than in controls (0-6 microg/l; mean +/- s.d. = 1.58 +/- 2.24; p = 0.04). Serum NSE levels in RD patients ranged from 6.5-80 microg/l (mean +/- s.d. = 26 +/- 21) and was significantly higher than in controls (5.3 +/- 1.66 microg/l; p = 0.005). CONCLUSIONS: Retinal neuron injury in retinal detachment (RD) releases sufficient Neuron Specific Enolase (NSE) to be detected in subretinal fluid, aqueous, and even in serum. Thus, NSE could index disease severity in RD and provide a means by which to assess the response to neuroprotection in RD.

Adult↗

Dynamic light scattering of diabetic vitreopathy.

BACKGROUND: Diabetes induces pathology throughout the body via nonenzymatic glycation of proteins. Vitreous, which is replete with type II collagen, undergoes significant changes in diabetes. The resultant diabetic vitreopathy plays an important role in diabetic retinopathy. Detecting these molecular changes could provide insight into diabetic eye disease as well as molecular effects elsewhere in the body. METHODS: Human eyes were obtained at autopsy and studied in the fresh, unfixed state. Sclera, choroid, and retina were dissected off the vitreous for dark-field slit microscopy and dynamic light scattering (DLS). For the former, the entire vitreous was exposed. For the latter, only a window at the equator was dissected in some specimens, and the anterior segment was removed leaving the posterior lens capsule intact in others. DLS was performed to determine particle sizes at multiple sites 0.5 mm apart, spanning the globe at the equator (window dissections) and along the antero-posterior axis. RESULTS: Dark-field slit microscopy in diabetic subjects detected findings typical of age-related vitreous degeneration, but at much younger ages than nondiabetic controls. Noninvasive DLS measurements found a greater heterogeneity and larger particle sizes in vitreous of subjects with diabetes as compared to age-matched controls. CONCLUSIONS: DLS can detect and quantify the early molecular effects that cause vitreous collagen fibrils to cross-link and aggregate. This could provide valuable insight into ocular and systemic effects of hyperglycemia, because the molecular changes in diabetic vitreopathy could serve as an index of such effects throughout the body. In addition to the diagnostic implications, this methodology could provide a rapid, reproducible way to monitor the response to therapy with novel agents intended to prevent the complications of diabetes on a molecular level.

Adult↗

Image enhancement improves reading performance in age-related macular degeneration patients.

We wanted to determine whether the 2- to 4-fold increases in reading speed found for patients with age-related macular degeneration (ARMD) when reading filtered text, presented one word at a time in the middle of the display would also be found when filtered text was scrolled across the screen. Reading speeds for filtered text that compensates for an observer's reduced contrast sensitivity function (CSF) were compared with the reading speeds for unfiltered text, when continuous, non-repeating text was scrolled across the display. The reading speeds of the ARMD observers tested were 1.7-4.5-times faster when reading filtered text, than when reading unfiltered text that was scrolled across the screen. The largest increments, over a 4-fold increase, were obtained in those subjects with the lowest unfiltered reading rates and the greatest loss of central vision. This study illustrates the usefulness of individualized text filtering for image enhancement in digitally based viewing devices to provide low vision remediation.

Aged↗

Relationship between prorenin, IGF-I, IGF-binding proteins and retinopathy in diabetic patients.

Plasma prorenin and renin, serum insulin-like growth factor I (IGF-I) and IGF-binding protein (IGFBP-2 and IGFBP-3) concentrations were measured in 22 randomly selected male and female patients with insulin-dependent diabetes mellitus (IDDM) or non-IDDM (NIDDM). Plasma prorenin concentration was significantly elevated in patients with proliferative retinopathy (1869.5 +/- 785.0 mUL-1, mean +/- SEM) compared to patients with nonproliferative retinopathy (325.5 +/- 73.2 mUL-1, P < 0.003) and those without retinopathy (318.6 +/- 47.3 mUL-1, P < 0.007). Similarly, serum insulin-like growth factor-I (IGF-I) concentration in patients with proliferative retinopathy (126.3 +/- 21.5 micrograms L-1) was significantly higher than in patients with nonproliferative retinopathy (126.3 +/- 14.85 micrograms L-1, P < 0.004) and without retinopathy (135.2 +/- 37.26, P < 0.05). There was moderately strong positive correlation between plasma prorenin and serum IGF-I concentrations (r = 0.56, P < 0.01). Plasma prorenin concentration was uninfluenced by change in renal function (creatinine clearance, serum creatinine or BUN), but IGF-I levels were inversely related to creatinine clearance (r = 0.67, P < 0.002). There was no demonstrable relationship between IGF-binding proteins and prorenin or renin concentrations. In view of some overlap between plasma prorenin and serum IGF-I concentrations in diabetic patients with proliferative and nonproliferative retinopathy, measurement of both markers may be more useful in predicting the development of proliferative retinopathy in patients with diabetes mellitus than either measurement alone.

Adult↗

Effects of pentoxifylline on choroidal blood flow in nonproliferative diabetic retinopathy.

OBJECTIVE: Diminished blood flow plays an important role in the progression of diabetic retinopathy. Since increased blood viscosity is a contributing factor to hypoperfusion, it was of interest to determine whether therapy intended to decrease blood viscosity and induce vasodilation could increase blood flow in patients with diabetic retinopathy. METHODOLOGY: Ten patients, 4 with nonproliferative diabetic retinopathy and 6 age-matched, nondiabetic controls, were studied by a noninvasive system to index choroidal blood flow. Pentoxifylline was administered daily at an oral dose of 400 mg tid in the diabetic patients for nine months. RESULTS: The control group had pulse amplitude = 2.87 +/- 0.67 mm Hg with pulsatile choroidal blood flow = 714 +/- 196 microL/minute. Reproducibility studies in the control group (6 patients measured on three separate occasions) demonstrated an intraclass correlation coefficient of reliability, r = 0.83. In the diabetic patients, pulsatile flow = 276 +/- 68 microL/minute, 61% lower than the age-matched nondiabetic subjects (P = 0.003). After nine months of pentoxifylline therapy the diabetic patients had an increase in pulsatile choroidal blood flow to 469 +/- 152 microL/minute (P < 0.002). CONCLUSIONS: Pentoxifylline therapy brought blood flow levels in the diabetic patients closer to those of the nondiabetic age-matched control population so that following therapy there was no statistically significant difference between the two groups although the former were still lower. The potential efficacy of pentoxifylline in improving ocular blood flow in patients with diabetic retinopathy should be tested in a large controlled clinical trial.

Adult↗

Raman spectroscopy of human vitreous in proliferative diabetic retinopathy.

PURPOSE: Recent studies have demonstrated increased nonenzymatic glycation in vitreous from patients with diabetic retinopathy. The present study reports the use of Raman spectroscopy as a novel approach for investigating these molecular changes in human vitreous and experimental tissues. METHODS: Near-infrared laser-excited Fourier-transform (FT) Raman spectroscopy (RS) was performed on vitreous specimens obtained at surgery from seven patients with proliferative diabetic retinopathy and from 10 controls. Measurements were also obtained from samples of control and glycated (in vitro) rat tail tendon collagen and demineralized chick bone collagen. RESULTS: Spectroscopy of vitreous samples from patients with diabetic retinopathy revealed two prominent peaks at 1604 cm-1 and 3057 cm-1, corresponding to aromatic C = C and C-H stretching vibrations in pi-conjugated and aromatic molecules. The peak at 1604 cm-1 was threefold higher in vitreous from patients with diabetes than from controls. Spectra obtained from experimental tissues provided evidence suggesting that the results obtained in human vitreous may be due to nonenzymatic glycation and not to the lysyl oxidase pathway. CONCLUSIONS: These findings suggest that human vitreous obtained from subjects with diabetes may be distinguished from control vitreous by FT-RS and that the peaks characterizing the diabetic samples are possibly due to nonenzymatic glycation. Raman spectroscopy may provide a useful method to elucidate the molecular events underlying these abnormalities.

Aged↗