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M T Coroneo

Publications and source records attributed to M T Coroneo.

At least 37 records · Page 2Linked to original sources
PubMed2000

Expression of MMPs and TIMPs in human pterygia and cultured pterygium epithelial cells.

PURPOSE: Pterygia are a common, benign, fibrovascular, and infiltrative process of the corneal-conjunctival junction of unknown pathogenesis. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes active against all components of the extracellular matrix, whose activity is specifically neutralized by tissue inhibitors of MMPs (TIMPs). In the current study the hypothesis was that MMPs and TIMPs may actively participate in the formation and progression of pterygia. METHODS: In this study, 25 pterygium specimens and 15 normal conjunctival biopsies obtained from subjects undergoing surgery for glaucoma and cataract, were processed for immunohistochemistry or in situ hybridization. Pterygium epithelial cells (PECs) were cultured under serum-free conditions and exposed to proinflammatory cytokines to determine both the mRNA and protein expression profiles of MMPs and TIMPs. RESULTS: Collagenase-1 and gelatinase A were expressed in all pterygia examined, specifically localized to the epithelium (directly adjacent to collagen type III), with gelatinase B expression exclusively associated with neutrophils. No collagenase-1 or gelatinase A was detected in normal conjunctiva. TIMP-1 and -3 were localized to epithelial cells with additional TIMP-3 immunoreactivity detected in the extracellular matrix, endothelial cells and leukocytes of all diseased tissue. TIMP-3 protein was evident in 4 of 15 normal conjunctiva. Induction of collagenase-1, gelatinase A, and TIMP-1 mRNA and protein was demonstrated in epithelial cells treated with tumor necrosis factor-alpha and interleukin-1alpha, whereas TIMP-3 expression was unaltered. CONCLUSIONS: This is the first study to document the cellular expression of MMPs and TIMPs in pterygia and cultured human PECs. MMPs and TIMPs may contribute to the inflammation, tissue remodeling, and angiogenesis that characterize pterygia. Understanding the role these proteins play may lead to novel therapies intended to reduce the progressive nature of pterygia.

Blotting, Western↗
PubMed2000

Differential expression of matrix metalloproteinases and their tissue inhibitors at the advancing pterygium head.

PURPOSE: Pterygia are a proliferative and inflammatory growth of limbal epithelial stem cell origin, characterized by corneal tissue invasion and extensive matrix remodeling including the destruction of Bowman's layer (BL). The purpose of this study was to determine the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) at the advancing pterygium edge. METHODS: Formalin-fixed, paraffin-embedded whole eyes (n = 11) with pterygia attached, were serially sectioned and analyzed immunohistochemically to determine the spatial distribution of four MMPs and three TIMPs. Tear samples were collected from other patients with pterygia (n = 11) and displayed by gelatin zymography. RESULTS: Collagenase-1 was expressed by pterygium epithelial cells, corneal stromal fibroblasts and pterygium fibroblasts that had migrated between the epithelium and BL at the advancing pterygium edge. Collagenase-3 and gelatinases A and B were detected in all pterygia, intensely staining columnar epithelial cells directly adjacent to the denatured BL. In addition, gelatinase A immunoreactivity was observed on BL. Immunoreactivity for TIMP-1 and -3 paralleled that of the gelatinases, with more intense staining in epithelial cells and fibroblasts where BL was absent. TIMP-2 was faintly detected in pterygium epithelial cells but intensely stained pterygium fibroblasts. Gelatinase B was the most abundant gelatinolytic enzyme present in tears, elevated approximately twofold in eyes with pterygia versus the contralateral control eyes. CONCLUSIONS: This investigation is the first to identify the expression pattern of MMPs and TIMPs at the advancing pterygium edge in specimens of human eyes and in tears derived from patients with pterygia. These enzymes may be responsible for the destruction of BL, and their pattern of differential expression suggests that each may play a selective role in the pathogenesis of pterygia.

Adult↗
PubMed1999

The pathogenesis of pterygia.

Pterygium is an active, invasive, inflammatory process, a key feature of which is focal limbal failure. In a two-stage process, "conjunctivalization" of the cornea occurs with tissue characterized by extensive chronic-inflammation, cellular proliferation, connective tissue remodeling, and angiogenesis. An understanding of this process has resulted in efforts aimed at limbal reconstruction, which is considered the gold standard for surgical care. Although good results have been obtained with other treatment methods, a long-term approach to follow-up with at least 5-year survival figures is desirable. Sophisticated analyses of the tear film and surface epithelium in patients with pterygium may help explain symptoms. The efficacy, at least in the short term, of nonsteroidal anti-inflammatory drugs in the treatment of inflamed pterygia has been confirmed. Corneal topographic analysis has shown that surgery reduces induced astigmatism and also causes subtle changes that may explain postsurgical improvements in vision.

Conjunctiva↗
PubMed1999

Culture and characterisation of epithelial cells from human pterygia.

BACKGROUND/AIMS: Pterygia are a common disorder of the ocular surface. The disease represents a chronic fibrovascular and degenerative process thought to originate at the conjunctival-corneal junction, where altered limbal stem cells are proposed to be the cell of origin. Extensive epidemiological evidence exists to implicate ultraviolet B irradiation in the pathogenesis of pterygia. To date no animal or in vitro culture model has been developed to test such an hypothesis. The aim of this study was to establish and characterise a pure population of epithelial cells derived from pterygium tissue. METHODS: Tissue specimens were obtained from patients undergoing pterygium excision. Explants were cultured in either serum free or serum supplemented medium. Primary and passaged cells were processed for light microscopy, analysed by flow cytometry, and characterised immunohistochemically using specific antibodies. RESULTS: In serum free culture, cuboidal cells with typical morphology of epithelial cells migrated from the pterygium explants from 3 days onwards and eventually formed a cohesive monolayer. Passaged cells consisted of 98.4% cytokeratin positive cells and demonstrated immunoreactivity for multiple cytokeratins, including AE1, AE3, AE5, but were negative for AE8. These cells also expressed an epithelial specific antigen, together with vimentin and mucin, as did epithelial cells in sections of pterygia. CONCLUSIONS: A relatively simple method of isolating pterygium epithelial cells has been established. Cultured pterygium epithelial cells are phenotypically and functionally similar to their in vivo counterparts with respect to keratin, vimentin, and mucin expression. In vitro assays using these cells may aid in elucidating the pathogenesis of pterygia.

Cells, Cultured↗
PubMed1998

High-dose (2000-microgram) intravitreous ganciclovir in the treatment of cytomegalovirus retinitis.

OBJECTIVE: The authors prospectively studied visual outcome, relapse, complications, and survival of patients with acquired immune deficiency syndrome (AIDS)-related cytomegalovirus (CMV) treated with high-dose intravitreous ganciclovir (2 mg/0.1 ml) injections. The outcomes were compared with those of patients treated with standard doses of intravenous ganciclovir in the same institution. The histopathologic and electrophysiologic effects of high-dose intravitreous ganciclovir injections in rabbits also were studied. DESIGN: A nonrandomized case series. PARTICIPANTS: A total of 42 patients (74 eyes) were treated with intravitreous injections and 18 patients (27 eyes) were treated with intravenous ganciclovir. Five eyes of three New Zealand white rabbits were injected with ganciclovir, and the sixth eye was a control specimen. INTERVENTION: Patients treated with intravitreous injections received twice-weekly doses of 2 mg/0.1 ml ganciclovir for 3 weeks, then weekly injections. Patients treated with intravenous ganciclovir received standard doses. Patients were monitored with regular examinations. Rabbit eyes were given intravitreous injections of 1 mg/0.1 ml of ganciclovir weekly for 4 weeks. MAIN OUTCOME MEASURES: Assessments of vision, retinal inflammation, and survival were made. Electroretinograms were performed on the rabbit eyes, and they were processed for light and electron microscopy. RESULTS: In the intravitreous group, visual acuity (VA) was stable in 64 of 74 eyes, 5 improved, and 5 deteriorated. Sixty-three (85%) of 74 eyes had final VA of 20/20 to 20/40. Relapse occurred in five eyes (7%; median time, 42 weeks). There were three cases of endophthalmitis. Median survival after diagnosis of CMV retinitis was 36 weeks. In the intravenous group, VA was stable in 18 eyes, 0 improved, and 9 deteriorated. Sixteen (59%) of 27 eyes had final VA of 20/20 to 20/40. Relapse occurred in 15 eyes (56%) at a median time of 21 weeks. Median survival was 21 weeks. The rabbit studies showed no evidence of toxicity. CONCLUSION: High-dose intravitreous ganciclovir effectively suppressed CMV retinitis, preserved vision, and prevented relapse without deterioration in survival.

AIDS-Related Opportunistic Infections↗
PubMed1998

The bionic eye (electronic visual prosthesis): a review.

The concept of a visual prosthesis for the blind or partially sighted is not a new one. Indeed, for more than three decades this technology based treatment for blindness has appeared imminent. Despite the concerted efforts of numerous physicians, scientists and engineers, the successful application of a useful visual prosthesis remains elusive. The present review will endeavour to describe past efforts, investigate the present state of the art and indicate the obstacles that must be overcome in order to bring an electronic visual prosthesis to fruition.

Bionics↗
PubMed1996

High dose intravitreal ganciclovir injection provides a prolonged therapeutic intraocular concentration.

BACKGROUND: Although intravitreal high dose ganciclovir has previously been found to provide excellent control of cytomegalovirus (CMV) retinitis, little was known about the vitreous concentrations of ganciclovir after a 2 mg intravitreal injection. METHODS: Eleven vitreous samples were taken from seven patients with CMV retinitis at 24 and 72 hours after a 2 mg intravitreal injection of ganciclovir and the concentration of ganciclovir was measured by high performance liquid chromatography. RESULTS: The mean concentration of ganciclovir at 24 hours was 143.8 mg/l (95% confidence interval 97.8-190) and at 72 hours was 23.4 mg/l (95% CI 0-49.7). The half life ranged from 11.9 to 26.3 (mean 18.8) hours in the four patients who had two samples taken. The mean half life calculated from the mean concentrations at 24 and 72 hours was 18.3 hours, so the calculated mean concentration at 7 days was 0.6 mg/l. CONCLUSIONS: This suggests that it takes about 7 days to eliminate the intravitreal ganciclovir, and that it is not likely to accumulate with weekly injections. The intravitreal concentrations achieved with high dose therapy remained above the ID50 for CMV (0.25-1.22 mg/l) for up to 7 days.

Antiviral Agents↗
PubMed1995

High dose intravitreal ganciclovir for CMV retinitis: a shelf life and cost comparison study.

BACKGROUND: It was previously found that high dose intravitreal ganciclovir provided superior treatment of cytomegalovirus retinitis compared with intravenous treatment. This study examined the stability and solubility of the ganciclovir solution to determine the shelf life of prepared solution, and compared the cost of intravitreal with intravenous therapy. METHODS: For the solubility studies high performance liquid chromatography was used to determine the ganciclovir concentration in various solutions. Measurements were taken of freshly made 20 mg/ml solution, the same solution stored at room temperature or frozen for 10, 17, and 24 days, after the solution was filtered, and after it was heated at 56 degrees C. For the cost comparison analysis the cost of 22 patients treated exclusively with intravitreal high dose ganciclovir was compared with cost estimates for the same patients treated with a standard intravenous therapy regimen over the same time. RESULTS: There was little variation in the concentration of ganciclovir regardless of the storage conditions, suggesting that the 20 mg/ml solution was very stable. The heating and filtering experiments suggest that maximum solubility was achieved both in the freshly prepared and thawed frozen stored solution. The total cost of the intravitreal treatment was Aus $172,435 and the estimate of intravenous treatment was Aus $490,521. This represents a total saving of $318,086 (65%), or $14,458 per patient. The average number of weeks of treatment for each patient was 27.9 (613 weeks/22 patients), so the saving per patient per year was $29,946. CONCLUSION: High dose intravitreal ganciclovir therapy may be administered in a very cost effective way, which along with its acceptability, safety, and clinical efficacy make it an attractive method of treatment of CMV retinitis.

Cytomegalovirus Retinitis↗
PubMed1994

A model for pterygium formation.

The formation of a pterygium is modelled using a population balance model of corneal and limbal epithelial production. Scattered light incident at the temporal limbus is focused at the nasal limbus with a peak intensity > or = 20 times. We hypothesize that this causes a focal alteration of corneal epithelial stem cells (which play a role in maintaining a barrier between corneal and conjunctival epithelia). Normative rabbit corneal data were used. Light-induced conjunctival epithelial proliferation was implemented by amplifying normal epithelial cell production along a nasal sector of the limbal circumference. A ten-fold normal peak in stimulation was assumed at the nasal zero azimuth (3 o'clock position in the right eye) with a quadratic attenuation to zero stimulation (normal) at the circumferential limits. Adjacent points on the outer limbus were assumed to be independent generators of epithelial cells that migrated in centripetal streams into the cornea. Normalization of the attrition rate for a net surface accumulation of the proliferating cells was embedded into the computational algorithm. The localized conjunctival mass was allowed to travel the predicted distance along the surface before the final shape was computed. The result shows a wing-shaped mass with a curved leading edge (corneal side). It is proposed that the initial biologic event in pterygium pathogenesis is an alteration of limbal stem cells due to chronic ultraviolet light exposure. The concomitant breakdown of the limbal barrier and subsequent conjunctivalization of the cornea explain the shape and formation of a primary pterygium.

Animals↗
PubMed1994

Influence of corneal shape on limbal light focusing.

PURPOSE: Light incident at the temporal cornea is focused by the peripheral anterior eye to the nasal limbus, the usual site of pterygium formation. Parameters that may contribute to observed individual variations in the degree of limbal light focusing were assessed. METHODS: Computer-assisted optical ray tracing techniques were applied to a human anterior segment model. The angle of incident light (theta, 95 degrees to 108 degrees posterior to the sagittal plane), corneal central radius of curvature (ro, 7.2 to 8.4 mm), and shape factor (p) were varied, and the effect on distal limbal intensity (I) was calculated. RESULTS: The magnitude of intensity peaks (Ipeak) is dependent on theta and ro. Steeper corneas have higher intensity peaks (Ipeak approximately 21.5X at ro = 7.2 mm, p = 0.75), and flatter corneas have lower intensity peaks (Ipeak approximately 8X at ro = 8.4 mm, p = 0.75) (cf Ipeak approximately 14X for a standard cornea, ro = 7.8 mm, p = 0.75). Anteroposterior location of intensity peaks is dependent on theta and ro. Steeper corneas have intensity peaks situated more anteriorly, whereas flatter corneas have more posteriorly placed peaks. Distal light distribution profiles demonstrate that intensity peaks are not always centrally located. At lower angles of incidence (theta = 100 degrees, ro = 7.8 mm, p = 0.75), peak intensity is located approximately 1 mm above and below the horizontal plane. The overall distribution (envelope) of light at the distal limbus is apparently independent of corneal shape. CONCLUSIONS: Differences in corneal topography can account for the clinical observation of individual variation in the degree of limbal light focusing. Whether individuals with corneas capable of developing intense limbal foci may be more predisposed to developing pterygium requires further study.

Anterior Eye Segment↗
PubMed1994

Removal of corneal foreign bodies: an instructional model.

A simple method for inflicting corneal foreign body injuries on bovine eyes is described and illustrated. The subsequent use of these eyes for teaching corneal and rust-ring removal is demonstrated. This method is suitable for instruction of large numbers of students and could be included in an undergraduate curriculum.

Animals↗