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Biomedical subjects

A J Bron

Publications and source records attributed to A J Bron.

At least 19 recordsLinked to original sources
PubMed2006

A hypothesis to suggest that light is a risk factor in glaucoma and the mitochondrial optic neuropathies.

The authors propose that light entering the eye interacts with retinal ganglion cell (RGC) axon mitochondria to generate reactive oxygen intermediates (ROI) and that when these neurons are in an energetically low state, their capacity to remove these damaging molecules is exceeded and their survival is compromised. They suggest that in the initial stages of glaucoma, RGCs exist at a low energy level because of a reduced blood flow at the optic nerve head and that in the mitochondrial optic neuropathies (MONs), this results from a primary, genetic defect in aerobic metabolism. In these states RGCs function at a reduced energy level and incident light on the retina becomes a risk factor. Preliminary laboratory studies support this proposition. Firstly, the authors have shown that light is detrimental to isolated mitochondria in an intensity dependent manner. Secondly, light triggers apoptosis of cultured, transformed RGCs and this effect is exacerbated when the cells are nutritionally deprived. Detailed studies are under way to strengthen the proposed theory. On the basis of this proposal, the authors suggest that patients with optic neuropathies such as glaucoma or at risk of developing a MON may benefit from the use of spectral filters and reducing the intensity of light entering the eye.

Apoptosis↗
PubMed2005

Gelatinous drop-like corneal dystrophy in a child with developmental delay: clinicopathological features and exclusion of the M1S1 gene.

AIMS: Gelatinous drop-like corneal dystrophy (GDLD) is an early-onset, autosomal recessive condition characterised by amyloid deposits within the cornea. We report the histopathological and molecular genetic findings in a Caucasian child with GDLD who also exhibited global developmental delay. METHODS: Bilateral lamellar keratoplasty was carried out at age 6 and 7 years. Tissue was fixed for light and electron microscopy, including immunoelectronmicroscopy. The coding region of the M1S1 gene was screened for mutations in the affected proband and available relatives, using DNA extracted from mouthwashes. RESULTS: Nodular deposits, which were present subepithelially and in the central superficial stroma, stained typically for amyloid with PAS and Congo red. A nodular deposit of amyloid, together with large amounts of lactoferrin and sparse amounts of keratoepithelin (betaig-h3), was present in the central superficial stroma, causing destruction of Bowman's layer and elevation of the thinned, degenerate epithelium. Around the deposit zone, the stroma exhibited large numbers of thick filamentous proteoglycan deposits. While the affected child was homozygous for a novel A1133 C single-nucleotide polymorphism (SNP) that resulted in an aspartic acid to alanine substitution at position 173 of the M1S1 coding sequence, this polymorphism was also found at relatively high frequency in a sample of normal controls, enabling exclusion of the M1S1 gene as the disease locus. CONCLUSION: Increased epithelial permeability in GDLD may be explained in part by an altered membrane permeability of the superficial epithelial cells. An association with developmental delay has not been reported previously.

Amyloid↗
PubMed2004

Functional aspects of the tear film lipid layer.

The lipid layer is an essential component of the tear film, providing a smooth optical surface for the cornea and retarding evaporation from the eye. The meibomian lipids which compose it are well adapted for this purpose. They form a thin, smooth film whose thickness, and probably composition, influences the rate of evaporation. Their melting range ensures sufficient fluidity for delivery to the tear film from the lid margin reservoirs, while the film itself may exhibit a higher viscosity at the cooler temperature of the ocular surface. The factors governing lipid film formation during the blink are not fully understood, but one view is that the polar lipids, interacting with the aqueous sub-phase of the tear film, spread in advance of the non-polar components, which form the bulk of the film. The meibomian lipids stabilise the tear film by lowering its free energy; they carry water into the film during its formation and interact with lipid-binding proteins in the aqueous phase, such as tear lipocalin. The lipocalins, complexed with other tear components, may also contribute to the high, non-Newtonian viscosity of the tear film and its low surface tension, features which are essential for tear film stability. Formation of the lipid film is a complex process. Lipid is delivered to the tear film in the up-phase of the blink, more from the lower than the upper reservoir. The lipid layer comes to a stop well after completion of the blink and remains relatively immobile until it is compressed in the down-phase of the blink that follows. Then, it either retains its structure in a series of subsequent blinks, or is completely re-constituted after mixing with the reservoir lipids. Delivery of meibomian lipid to the marginal reservoirs is mainly the result of continuous secretion, under neural and hormonal control, supplemented by lid action. The reservoirs provide a hydrophobic barrier to tear overspill and to contamination by skin lipids which might destabilise the tear film. They probably also provide the chief route for meibomian lipid excretion.

Adolescent↗
PubMed2004

The contribution of meibomian disease to dry eye.

The tear film lipid layer is the major barrier to evaporation from the ocular surface. A decrease in its thickness or functional integrity may cause evaporative dry eye (EDE). Obstructive meibomian gland dysfunction (MGD) is the most common cause of EDE and occurs as a primary disorder or secondary to acne rosacea, seborrheic or atopic dermatitis, and with cicatrizing conjunctival disorders, such as trachoma, erythema multiforme, and cicatricial pemphigoid. MGD may be an incidental finding in asymptomatic eyes, or it may be responsible for irritative lid symptoms in the absence of dry eye. MGD-dependent EDE is diagnosed on the basis of a defined degree of MGD in a symptomatic patient showing typical ocular surface damage in the absence of an aqueous tear deficiency. When MGD occurs in a background of aqueous tear deficiency (ATD), then an additional evaporative component may assumed, depending on the extent of meibomian obstruction. However, definitive criteria are not yet established. The clinical severity of dry eye is greatest when ATD and EDE occur together, particularly in Sjogren syndrome. A hypothesis is proposed to explain the steps leading to primary, simple MGD and subsequent EDE.

Journal Article↗
PubMed2004

Clinical and ultrastructural findings in mare's tail lines of the corneal epithelium.

AIMS: Mare's tail lines are uncommon, grey, parallel, tapering epithelial lines, which may give rise to discomfort or to visual symptoms. The authors report the clinical and ultrastructural findings in two patients METHODS: Therapeutic debridement was performed in two patients suffering from mare's tail disorder. The loosely attached epithelium was removed and fixed in glutaraldehyde containing cuprolinic blue and processed in a standard fashion for electron microscopy. RESULTS: Ultrastructural studies showed an avascular, collagenous pannus extending under the whole of the excised epithelium in each case and separated from it by a thickened basal lamina like zone. The basal laminar material extended into the epithelium in folds, in keeping with the clinical features. Interesting ultrastructural features included: (1) a lack of hemidesmosomes in relation to the basal laminar material; (2) trapping of degenerate keratocytes within the invaginating basal laminar folds; (3) an unusual regularity and fine dimensions of the collagen fibrils and proteoglycans making up the subepithelial pannus. The basal laminar material contained proteoglycans and small fibres similar in appearance to long spacing collagen. CONCLUSIONS: Mare's tail lines are caused by basal laminar material, assumed to be chiefly of epithelial origin, which invaginates the corneal epithelium. The presence of occasional keratocytes within the invaginating folds suggests that there may be a stromal contribution to the disorder. The visibility of mare's tail lines in the focal beam of the slit lamp is likely to be related to the thickness and light scattering properties of the invaginations and of the subepithelial deposits. Tractional forces, imposed by lid action, could explain their horizontal disposition.

Aged↗
PubMed2003

Differential effects of aging on transport properties of anterior and posterior human sclera.

The transport properties and composition of 44 pairs of human sclera, 37-91 years were compared. Solute transport, diffusion and partition coefficients of posterior sclera for solutes ranging in mass from 0.023-70kDa were higher than those of anterior sclera; the posterior region was also more hydrated. The differences in partition coefficient between anterior and posterior sclera became more pronounced as solute molecular weight increased. Partition coefficients and hydration of both regions decreased with increasing age. Chondroitinase ABC digestion, which removed the majority of glycosaminoglycans, increased partition coefficients of both regions significantly. These results suggest that for regions of equal scleral thickness, neglecting the influence of vascular factors, drug delivery will be more readily achieved across the posterior sclera than the anterior sclera in the age group studied and that, for both regions, ease of delivery will decrease with decreasing age.

Adult↗
PubMed2001

Diagnosis of dry eye.

Dry eve disease is characterized by symptoms, ocular surface damage, reduced tear film stability, and tear hyperosmolarity. There are also inflammatory components. These features can be identified by various kinds of diagnostic tests (symptom questionnaires, ocular surface staining, tear break-up time, and osmometry), although there may not be a direct correlation between the number or severity of symptoms and the degree of ocular surface damage or tear deficiency. Once the diagnosis of dry eye disease has been established, further tests can be used to classify the condition into tear-deficient or evaporative dry eve. The two forms of dry eye are not mutually exclusive and often co-exist. The optimal diagnosis of dry eye disease, therefore, depends on the results of several tests, and this article suggests an appropriate order for performing these tests at a single clinic visit.

Diagnostic Techniques, Ophthalmological↗
PubMed2001

Posterior subcapsular and nuclear cataract after vitrectomy.

PURPOSE: To examine the morphological changes in the postvitrectomy lens and to monitor the development of these changes over time. SETTING: Oxford Eye Hospital, Oxford, United Kingdom. METHODS: In this prospective study, 33 consecutive phakic patients having pars plana vitrectomy were recruited. Cataract development was quantified by clinical grading and digital Scheimpflug image analysis. Slitlamp biomicroscopy and photography were used to document the morphological appearance. The main outcome measures were the incidence, morphology, and development of posterior subcapsular and nuclear cataract. RESULTS: A characteristic, transient posterior subcapsular cataract (PSC) was present in 89% (17 of 19) of tamponade patients within 24 hours of surgery. Of the patients who had vitrectomy without tamponade, 9% (1 of 11) developed similar changes. Nuclear opacity developed in 61% (11 of 18) of tamponade patients and in 50% (3 of 6) of nontamponade patients. A longer term retrospective review of the same patients' case notes revealed nuclear cataract in 67% (12 of 18) of tamponade cases and 30% (3 of 10) of nontamponade cases. Eighteen percent (2 of 11) of nontamponade cases and 67% (14 of 21) of tamponade cases had cataract surgery after a 10.7 month and a 12.4 month follow-up, respectively. CONCLUSIONS: Vitrectomy and tamponade produced a characteristic transient PSC in the immediate postoperative period. Disruption of fluid balance in the region of the posterior lens was suggested by the morphological appearance. The acute changes resolved but were followed by accelerated nuclear opacification.

Aged↗
PubMed2001

Congenital hereditary endothelial dystrophy and band keratopathy in an infant with corpus callosum agenesis.

PURPOSE: To report the features of a syndrome of endothelial failure and band-shaped keratopathy in an infant with corpus callosum agenesis. METHODS: The clinical and histopathologic features of an infant presenting with bilateral corneal clouding and corpus callosum agenesis are reported. The patient underwent bilateral penetrating keratoplasty at ages 28 months and 4 years. Light and electron microscopy were used to characterize the structural changes. RESULTS: The epithelium was thin and degenerate. Bowman's membrane contained spherical aggregates that were present also within a connective tissue pannus. The midstroma was normal, but there were floral and rope-like aggregations of collagen in the pre-Descemet's membrane region. Under electron microscopy, the spherules formed target-shaped lesions with a central focus of alternating electron-dense and lucent material. Numerous microfilaments in the pannus and anterior stroma labeled with fibrillin-1 antibody. Microfilaments within fibroblasts were stained with vimentin antibody. Posteriorly, the endothelium was mainly absent and Descemet's membrane showed a fetal layer and a posterior collagenous layer. CONCLUSION: Corneal appearances in this patient were in keeping with those of congenital hereditary endothelial corneal dystrophy. However, there was no family history and neither parent showed a clinical endothelial abnormality. The presence of fetal, banded material in Descemet's membrane suggested that endothelial loss began at or near the time of birth. The band keratopathy was regarded as a secondary change. The association with corpus callosum agenesis does not appear to have been described previously.

Agenesis of Corpus Callosum↗
PubMed2001

Intraocular vancomycin levels after intravitreal injection in post cataract extraction endophthalmitis.

PURPOSE: Intravitreal antibiotics are the mainstay of treatment of endophthalmitis following cataract surgery. The purpose of this study is to determine the range of intraocular vancomycin found after intravitreal therapy and assess the optimum time for repeat injections. METHODS: Aqueous and vitreous vancomycin was assayed at the time of reinjection in 14 patients with endophthalmitis showing a poor clinical response after their primary injection. Nine patients received vancomycin 2 mg and another five received vancomycin 1 mg. In six patients the injection was repeated at 48 hours and in seven at 72 hours. Two patients received three injections. RESULTS: Aqueous vancomycin varied from 8.4 to 170 mg/L and the vitreous vancomycin level ranged from 21.2 to 220 mg/L. CONCLUSIONS: In the current study vitreous vancomycin levels were variable, but well within the therapeutic range for sensitive Gram-positive organisms. At times they exceeded the putative retinotoxic levels (100 mg/L). Higher aqueous levels were found after an injection of 2 mg than after 1 mg. Vancomycin levels were still very high 3 days after injection of 2 mg where results were available. Assay at the time of repeat injection may provide insight into the adequacy of vitreous levels and guide future therapy.

Aged↗
PubMed2001

Ultrastructural morphology and expression of proteoglycans, betaig-h3, tenascin-C, fibrillin-1, and fibronectin in bullous keratopathy.

AIMS: To investigate the ultrastructural localisation of proteoglycans (PG), betaig-h3 (keratoepithelin), tenascin-C (TN-C)), fibrillin, and fibronectin in bullous keratopathy (BK) corneas. METHODS: Five corneas from cases of pseudophakic bullous keratopathy (BK) were examined by electron microscopy. PG were demonstrated using cuprolinic blue, and the proteins betaig-h3, TN-C, fibrillin, and fibronectin were immunolocalised with rabbit anti-betaig-h3, mouse anti-TN-C (BC10 and TN2), mouse anti-fibrillin-1 (MAB2502), mouse anti-fibrillin (MAB1919), and rabbit anti-fibronectin by using a standard immunogold technique. RESULTS: Epithelial cells contained numerous vacuoles. Epithelial folds and large, electron lucent subepithelial bullae were present. Basal lamina was thickened and traversed by disrupted anchoring filaments. In the stroma, interfibrillar collagen spacing was increased and abnormally large PG were present. Descemet's membrane (DM) contained lucent spaces in which there were small filaments. Keratocyte and endothelial cells contained melanin granules. A posterior collagenous layer (PCL) contained numerous microfilaments and wide spacing collagen fibres with a periodicity of 100 nm. Large quantities of abnormal PG were observed at the endothelial face of the PCL. Very strong labelling with betaig-h3 antibody was observed in the basement membrane, Bowman's layer, stroma, DM, and PCL, but not in keratocytes and endothelial cells. Strong labelling with BC10 and TN2 was seen below the epithelium, in electron lucent spaces where the hemidesmosomes were absent, in the fibrotic pannus, in parts of Bowman's layer, the stroma, and Descemet's membrane. Labelling with BC10 was stronger and more evenly distributed than with TN2. Fibrillin-1 (MAB2502) and fibrillin (MAB1919) labelling was similar to TN-C labelling. Fibrillin (MAB1919) labelling was stronger than fibrillin-1 (MAB2502) labelling. CONCLUSIONS: Immunoelectron microscopy showed precise labelling of proteins at both the cellular and the subcellular level. Expression of proteins betaig-h3, TN-C, fibrillin, and fibronectin was highly increased compared with normal cornea. In the oedematous stroma, increased collagen fibril separation may facilitate a wider distribution of some soluble proteins, such as betaig-h3, throughout stroma. The modified expression of the proteins studied in these cases of BK may be regarded as part of an injury response.

Aged↗
PubMed2000

The effect of hydration and matrix composition on solute diffusion in rabbit sclera.

There is increasing interest in the possibility for drug delivery into the vitreous humor across the conjunctiva and sclera as an alternative route to the conjunctiva-cornea pathway. As a preliminary to human studies we have investigated the influence of scleral composition and hydration on solute transport in the rabbit sclera. Intermuscular sclera was excised from adult New Zealand rabbits. Tissue samples were either examined directly (controls), digested using chondroitinase ABC or crosslinked using glutaraldehyde. The effect of these treatments on the ultrastructural appearance of the sclera was assessed. Diffusion and partition coefficients for solutes of different molecular weights [sodium chloride (23 MW),(14)C sucrose (342 MW) and dextran-fluoresceins (3, 10, 40 and 70 kDa)] were measured in relation to tissue treatment. The results were used to determine the effect of tissue structure and composition on solute movement. We have found that: (1) diffusion and partition coefficients are sensitive to solute MW, decreasing as MW increases; (2) diffusion and partition coefficients are sensitive to tissue hydration, increasing as hydration increases; (3) crosslinking of the sclera by glutaraldehyde reduced the partition coefficients significantly for solutes with MW over 3 kDa; and (4) removal of glycosaminoglycans has only a small effect on either diffusion or the partition coefficient.

Animals↗
PubMed2000

5-Hydroxytryptamine1A agonists: potential use in glaucoma. Evidence from animal studies.

Various classes of compounds exist to lower intraocular pressure (IOP) in the treatment of glaucoma. None of them is ideal since some patients respond better than others and the side effects vary between individuals. New classes of compounds need to be introduced to allow the clinician greater scope for effective treatment of all patients. It is now generally agreed that the cause of ganglion cell dysfunction in glaucoma is likely to be multifactorial and that concentrating solely on reducing IOP is inadequate. Irrespective of the reason for the dysfunction, the future goal must be to attenuate cell death. This may be achieved with drugs that interact with components of the retina, and is termed 'neuroprotection'. Thus, drugs that can both reduce IOP and act as neuroprotectants would be ideal for the treatment of glaucoma. In this article we summarise studies on animals which show serotonergic 5-HT1A agonists to both reduce IOP when topically applied to the rabbit eye and blunt the damaging effect to the rat retina and ganglion cells induced by glutamate toxicity or ischaemia. Reduction of IOP occurs via stimulation of 5-HT1A receptors associated with the ciliary processes. Neuroprotection of retinal neurones appears to involve the interaction of 5-HT1A agonists with membrane sodium channels and/or 5-HT1A or even possibly 5-HT7 receptors. Various 5-HT1A agonists are used in patients to treat depression, so classes of these drugs have a proven safety profile for use in patients. The animal studies summarised in this article suggest that 5-HT1A agonists need to be considered as a new class of drugs for the treatment of glaucoma.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2000

Post-operative changes in the capsulorhexis aperture: a prospective, randomised comparison between loop and plate haptic silicone intraocular lenses.

PURPOSE: There is disagreement regarding whether the capsulorhexis aperture always decreases or may increase post-operatively. The aim of this study was to settle the controversy concerning loop haptic silicone lenses and to learn more of the dynamics of the capsulorhexis relating to plate haptic lenses. METHODS: We performed a prospective randomised study comparing the post-operative changes in capsulorhexis aperture in two groups of eyes implanted with either plate or loop haptic silicone intraocular lenses. All the surgery was performed, at a teaching hospital in the United Kingdom, by a single surgeon, using a standard technique of phacoemulsification. Patients were reviewed at 2 weeks and 6 months post-operatively. Digital retroillumination images of the anterior segment were captured. The area of the capsulorhexis aperture was determined by manually detecting its edge on a computer monitor. RESULTS: Forty-eight cases were randomised. The groups were comparable for demographic variables and mean initial aperture size (p > 0.05). There was an 8.4% mean decrease in aperture size for the loop haptics, contrasting with 4.5% expansion for the plate haptics (p < 0.05). Sixty-five per cent of patients with the plate haptic underwent enlargement of the aperture, contrasting with 25% for the loop haptic lens (p < 0.05). CONCLUSIONS: Silicone lenses with plate haptics undergo expansion of the capsulorhexis aperture more frequently than those with Prolene loop haptics.

Aged↗
PubMed2000

Reflective meniscometry: a new field of dry eye assessment.

PURPOSE: To report a newly developed noninvasive method to measure the radius of tear meniscus curvature (reflective meniscometry) and its application to normal eyes, dry eyes, and other ocular surface conditions. METHODS: Two types of meniscometer--photographic and video--were devised. Both use tear meniscus as a concave mirror, and a specular reflex of an illuminated target at the meniscus was photographed or videotaped to obtain the radius of tear meniscus curvature. The photographic system was applied to 45 normal and 32 dry eyes; in the dry eyes, the radius of tear meniscus curvature was compared to the results of other dry eye examinations. The video system was used to examine meniscus formation on the ocular surface in patients with ocular surface irregularities. RESULTS: The radii of tear meniscus curvature were significantly lower in dry eyes (0.250 +/- 0.086 mm, mean +/- SD) than in normal eyes (0.365 +/- 0.153; p = 0.0003). There were significant correlations between the radius and fluorescein staining score (p = 0.0032) and the grading of interference colors on the precorneal oil film (p = 0.0125). Videomeniscometry demonstrated the tear meniscus to be very stable and proved to be useful in the study of menisci at the edge of rigid contact lenses and other menisci encountered in ocular surface disorders. CONCLUSIONS: Measurement of the radius of tear meniscus curvature may be useful in the diagnosis of dry eyes. Reflective meniscometry is expected to find wide applications in the analysis of tear meniscus in ocular surface disorders.

Diagnostic Techniques, Ophthalmological↗
PubMed2000

Genetics of the corneal dystrophies: what we have learned in the past twenty-five years.

PURPOSE: To indicate important changes in our understanding of the corneal dystrophies. METHODS: A review of the literature of the last quarter of a century. RESULTS: The earliest clinical classifications of the corneal dystrophies were based on the application of clinical, biological, histochemical, and ultrastructural methods. Since then, the first great impetus to our understanding has come from the application of techniques to map disorders to specific chromosome loci, using polymorphic markers. More recently, using candidate gene and related approaches, it has been possible to identify genes causing several of the corneal dystrophies and the mutations responsible for their phenotypic variation. A notable success has been to show that several important "stromal" dystrophies result from mutations in the gene beta ig-h3, which encodes for the protein keratoepithelin (beta ig-h3). CONCLUSIONS: For the corneal dystrophies, as with other inherited disorders, there is room for two sorts of classification system, one based mainly on clinical presentation and the other on an up-to-date understanding of the genetic mechanisms. They are not mutually exclusive. Some developmental corneal disorders are also discussed.

Cornea↗