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Biomedical subjects

Peng T Khaw

Publications and source records attributed to Peng T Khaw.

At least 19 recordsLinked to original sources
PubMed2006

Laser peripheral iridotomy in primary angle-closure suspects: biometric and gonioscopic outcomes: the Liwan Eye Study.

PURPOSE: To assess the immediate effect of laser peripheral iridotomy (LPI) and mechanisms of angle closure in a population-based study of primary angle closure (PAC) suspects. DESIGN: Prospective interventional study. PARTICIPANTS: People identified as PAC suspects aged 50 to 79 years from a population-based survey in Guangzhou, China. INTERVENTION: Laser peripheral iridotomy was performed in 1 randomly selected eye. Examinations were carried out before and 2 weeks after the intervention. MAIN OUTCOME MEASURES: Intraocular pressure (IOP), ultrasound biometry, optical pachymetry, and gonioscopy. RESULTS: A total of 72 people with bilateral suspected PAC participated in the study. Mean IOP decreased by 3 mmHg (P<0.001), but axial anterior chamber depth did not change significantly (P = 0.784) after LPI. Median limbal anterior chamber depth increased from 15% to 25% of peripheral corneal thickness (P<0.001, Wilcoxon signed-rank test). Median iridotrabecular angle width increased from 0 degrees to 10 degrees in the superior quadrant and from 10 degrees to 30 degrees in the inferior quadrant (P<0.001). Nevertheless, 14 eyes (19.4%) still had 3 or more quadrants in which the posterior (usually pigmented) trabecular meshwork could not be seen after laser iridotomy. CONCLUSIONS: This study confirms that LPI results in a significant increase in the angle width in Chinese people with narrow angles. However, one fifth of eyes had residual angle closure after LPI. Although this report confirms that iridotomy widens the anterior chamber angle in most PAC suspects, long-term prospective studies with a larger sample size are required to determine if the risks of PAC glaucoma and other related pathologic sequelae are reduced after prophylactic LPI and to investigate the risk-to-benefit ratio before recommending widespread use of prophylactic LPI in this population.

Aged↗
PubMed2006

Detection of narrow angles and established angle closure in Chinese residents of Singapore: potential screening tests.

PURPOSE: To assess the performance of peripheral and central anterior chamber depth (ACD) measurements, and autorefraction, in identifying Chinese people with occludable drainage angles or established primary angle closure. DESIGN: Population-based cross-sectional analysis. METHODS: Subjects aged 40 years and older were drawn from a representative sample of Chinese Singaporean residents. Limbal chamber depth (LCD) was estimated and central ACD was measured using optical pachymetry and ultrasound. An autorefraction was taken for all subjects. Angle width and the presence of peripheral anterior synechiae were determined by gonioscopy. Receiver operating characteristic curves were generated to show the performance of these tests in detecting occludable angles. RESULTS: A total of 1090 subjects were examined. The prevalence of occludable angles was 6.5%. LCD measurement performed best in detecting occludable angles (area under the curve [AUC] 0.904, 95% confidence interval [CI] 0.870, 0.937). Optical pachymetry and ultrasound measurement of ACD performed less well (AUC 0.859 and 0.810, respectively), and autorefraction performed poorly in detecting occludable angles (AUC 0.632). LCD also gave the best performance in detecting primary angle closure (AUC 0.782, 95% CI 0.727, 0.837). CONCLUSIONS: Limbal LCD estimation outperforms other methods of measuring ACD as a screening tool for the detection of occludable drainage angles in the Chinese population of Singapore.

Adult↗
PubMed2006

A novel homeobox mutation in the PITX2 gene in a family with Axenfeld-Rieger syndrome associated with brain, ocular, and dental phenotypes.

Axenfeld-Rieger Syndrome (ARS) is a genetically heterogeneous birth defect characterized by malformation of the anterior segment of the eye associated with glaucoma. Mutation of the PITX2 homeobox gene has been identified as a cause of ARS. We report a novel Arg5Trp missense mutation in the PITX2 homeodomain, which is associated with brain abnormalities. One patient had a small sella turcica likely to reflect hypoplasia of the pituitary gland and consistent with the critical role identified for Pitx2 in pituitary development in mice. Two patients had an enlarged cisterna magna, one with a malformed cerebellum, and two had executive skills deficits one in isolation and one in association with a below average intellectual capacity. The mutation caused a typical ARS ocular phenotype. All affected had iris hypoplasia, anterior iris to corneal adhesions, and corectopia. The ocular phenotype varied significantly in severity and showed some asymmetry. All affected also had redundant peri-umbilical skin, a hypoplastic maxilla, microdontia, and hypodontia missing between 20 and 27 teeth with an unusual pattern of tooth loss. Dental phenotypes were documented as they are often poorly characterized in ARS patients. All affected individuals showed an absence of first permanent molars with variable absence of other rarely absent teeth: the permanent upper central incisors, maxillary and mandibular first and second molars, and the mandibular canines. Based on the distinctive dental anomalies, we suggest that the dental phenotype can assist in predicting the presence of a PITX2 mutation and the possibility of brain abnormalities.

Abnormalities, Multiple↗
PubMed2006

Effect of trabeculectomy on lens opacities in an East Asian population.

OBJECTIVE: To examine the progression of lens opacity in Asian people after trabeculectomy and determine associated risk factors. METHODS: This was an observational case series of 243 people aged 36 to 82 years. Trabeculectomy was performed on 1 eye of each subject. Lens opacity was measured yearly using the Lens Opacification Classification System III. The main outcome measure was worsening of lens opacity defined as an increase of 2 or more Lens Opacification Classification System III units in any of the 3 lens regions, nuclear, cortical, and posterior subcapsular. Risk of progression was evaluated using logistic regression models. RESULTS: Data for 177 people were analyzed. One hundred seventeen (66%) of 177 subjects showed progression in opacity in any lens region at 3 years. Seventy-seven (66%) of 117 of those who progressed did so during the first year. Of these, 63 (82%) of 77 had lens opacity in the posterior subcapsular region. Factors associated with progression of posterior-subcapsular lens opacity at 1 year were diabetes (odds ratio, 2.4; 95% confidence interval, 1.0-5.4), use of antiglaucoma medication, dosage of topical steroid postoperatively, and being operated on by a trainee surgeon (odds ratio, 2.3; 95% confidence interval, 1.0-5.2). CONCLUSIONS: Trabeculectomy is associated with progression of lens opacity predominantly in the posterior subcapsular region. Modification of risk factors such as postoperative steroid use may delay progression.

Adult↗
PubMed2006

Failure of medical therapy despite normal intraocular pressure.

The disease glaucoma is now defined by characteristic optic disc and visual field change, without specific reference to the intraocular pressure (IOP). Success of treatment is no longer judged by the mere attainment of IOP less than 21 mmHg. Controversy remains, however, in deciding appropriate management where optic disc and/or visual field damage continues to progress despite a 'normal' IOP having been achieved with medical treatment. A panel of international glaucoma experts has provided management recommendations in four clinical scenarios--open-angle glaucoma, open-angle glaucoma in a myopic contact lens wearer, uveitic glaucoma and open-angle glaucoma in combination with visually significant cataract--where optic nerve and visual field progression has continued despite an IOP less than 21 mmHg on full medical treatment. Surgical intervention with mitomycin trabeculectomy is the most favoured further therapy.

Adult↗
PubMed2006

Human serum reduces mitomycin-C cytotoxicity in human tenon's fibroblasts.

PURPOSE: To determine the effect of human serum factors on mitomycin-C (MMC) cytotoxicity in cultured human subconjunctival Tenon's capsule fibroblasts. METHODS: Fibroblast monolayers were treated with 5-minute applications of mitomycin-C (0.4 mg/mL) and incubated in culture medium with or without additional human serum. Fibroblast apoptosis was quantified by direct cell counts based on nuclear morphology, flow cytometry with annexin-V/propidium iodide, and a lactate dehydrogenase release assay. The number of viable fibroblasts and fibroblast proliferation were measured with a colorimetric MTT assay and by bromodeoxyuridine (BrdU) labeling. RESULTS: Mitomycin-C induced significant levels of fibroblast apoptosis. The addition of human serum resulted in a 40% reduction in MMC-induced fibroblast apoptosis (range, 31.3%-55.3%; P = 0.021) as determined by nuclear morphology and a 32.4% reduction measured by annexin-V/PI. There was a corresponding dose-dependent increase in the number of viable fibroblasts. Serum did not restore proliferation in MMC-treated fibroblasts. CONCLUSIONS: Factors present in human serum reduce MMC cytotoxicity in cultured human Tenon's fibroblasts. Human serum increased the number of viable fibroblasts by inhibiting MMC-induced fibroblast apoptosis. Serum factors access aqueous humor after trabeculectomy and may therefore influence the clinical outcome of MMC treatment.

Annexin A5↗
PubMed2006

Prevalence and clinical characteristics of glaucoma in adult Chinese: a population-based study in Liwan District, Guangzhou.

PURPOSE: To assess the prevalence and mechanism of glaucoma in adults living in an urban area of southern China. METHODS: Random clustering sampling was used to identify adults aged 50 years and over in Liwan District, Guangzhou. Glaucoma was diagnosed with the ISGEO (International Society of Geographical and Epidemiological Ophthalmology) classification scheme. All subjects underwent gonioscopy. RESULTS: In the study, 1504 subjects (75.3% participation rate) were examined, with a crude prevalence of all glaucoma of 3.8% (95% confidence interval [CI], 2.8%-4.8%). Primary open-angle glaucoma (POAG) was found in 2.1% (95% CI, 1.4%-2.8%) and primary angle-closure glaucoma (PACG) in 1.5% (95% CI, 0.8%-2.1%). The prevalence of all glaucoma was significantly higher in older people and men. CONCLUSIONS: POAG was more common than PACG in this southern Chinese population, with rates similar to those reported in Chinese Singaporeans. The age-adjusted rate of POAG was similar to that found in European-derived populations, but PACG was more common among Chinese, indicating that there is a large burden of glaucoma in the Chinese people.

Age Distribution↗
PubMed2006

Gonioscopy in adult Chinese: the Liwan Eye Study.

PURPOSE: To assess gonioscopic characteristics of the drainage angle in adult Chinese in an urban area of southern China. METHODS: Clustered random sampling was used to select adults aged 50 years and older in Liwan District, Guangzhou. Gonioscopy was performed on all the subjects. The geometric angle width was graded in the superior and inferior quadrants, according to the Spaeth system. In addition, apparent and true iris insertion was classified in four quadrants with static and dynamic gonioscopy. The peripheral iris profile was described as steep, regular, concave, and plateau. Data are presented for all phakic right eyes. Secondary or iatrogenic cases were excluded in the analysis of peripheral anterior synechiae (PAS). RESULTS: Among 1405 participants in the study, data from 1330 (95%) right eyes were available for analysis. Iridotrabecular angles (ITA) < or =20 degrees were present in 36.9% (95% CI: 34.3%-40.0%) of eyes superiorly and in 27.9% (95% CI: 25.5%-30.4%) inferiorly. Narrower ITAs were more common in the older people (sex-adjusted odds ratio [OR] = 1.1 per year of life; P < 0.001) and the women (age-adjusted OR = 2.5, P < 0.001). Apparent iris insertion of grade A or B (with pigmented trabecular meshwork not visible) by quadrant was observed in 27.2% superiorly, 12.0% nasally, 7.7% inferiorly, and 14.2% temporally. Narrow angles (in which pigmented trabecular meshwork was not visible in three or more quadrants) were identified in 11.0% (95% CI: 9.3%-12.7%) of right eyes. Overall, 33.3% of eyes had a steep iris profile, 54.2% were normal, 2.7% were concave, and 10.1% were graded plateau. PAS were seen in 30 of 146 (20.5%) eyes with narrow angles and in 7 (0.6%) of 1184 eyes with angles that did not meet criteria for narrow angles. PAS were more likely with narrower angles, with 0%, 0.3%, and 1.9% of eyes with a mean ITA of 40 degrees, 30 degrees, and 20 degrees, respectively, having PAS as opposed to 12.6% and 27.5% for those with ITA 10 degrees and 0 degrees , respectively. CONCLUSIONS: Ten percent of this population of southern Chinese persons 50 years of age and older had narrow angles. PAS were present in one fifth of these people. From these cross-sectional data, it is unclear which of these individuals are at highest risk of the development of primary angle-closure (PAC) glaucoma. Longitudinal studies are necessary to determine appropriate strategies for preventing this potentially blinding outcome.

Aged↗
PubMed2005

Anterior chamber depth and the risk of primary angle closure in 2 East Asian populations.

OBJECTIVE: To evaluate the risk of peripheral anterior synechiae (PAS) and glaucomatous optic neuropathy attributable to primary angle closure at varying anterior chamber depths (ACDs) in two East Asian populations. METHODS: Participants 40 years and older were from 2 population-based glaucoma surveys in Mongolia and Singapore. Central ACD was measured by optical pachymetry. Presence of PAS was determined by dynamic gonioscopy. Cases with secondary PAS were excluded. Glaucomatous optic neuropathy was diagnosed in subjects with structural and functional evidence of glaucoma. RESULTS: A total of 2032 subjects, consisting of 942 Mongolians and 1090 Chinese Singaporeans, were included in this study. A logistic model of the relationship between ACD and PAS among Singaporeans showed a consistent, incremental increase in PAS across the entire range of ACD. In deeper anterior chambers the rate of PAS exceeded that seen in Mongolians. In Mongolians, there was a clear threshold for ACD (2.4 mm) at or above which PAS were very uncommon. With ACD less than 2.4 mm, the rate of PAS rose rapidly to overtake that seen in Singaporeans. CONCLUSIONS: Shallow anterior chambers are a significant risk factor for angle closure in East Asians, although the nature of the association is specific to the individual population. There was a trend toward higher rates of glaucomatous optic neuropathy in people with the shallowest anterior chambers.

Adult↗
PubMed2005

Matrix metalloproteinase-1 associates with intracellular organelles and confers resistance to lamin A/C degradation during apoptosis.

Since the first description of matrix metalloproteinase (MMP)-1 as an interstitial collagenase, great importance has been ascribed to this enzyme in extracellular matrix remodeling during tumoral, inflammatory, and angiogenic processes. As more evidence for the role of MMPs in targeting nonmatrix substrates emerges, casual observations that intracellular MMP-1 is found in vitro and in vivo prompt investigation of the role that MMP-1 may play on basic cell functions such as cell division and apoptosis. Here we show for the first time that MMP-1 not only has extracellular functions but that it is strongly associated with mitochondria and nuclei and accumulates within the cells during the mitotic phase of the cell cycle. On induction of apoptosis, MMP-1 co-localized with aggregated mitochondria and accumulated around fragmented nuclei. Inhibition of this enzyme by RNA interference or treatment with a broad MMP inhibitor caused faster degradation of lamin A, activation of caspases, and fragmentation of DNA when compared with untreated cells. These observations strongly suggest that intracellular association of MMP-1 to mitochondria and nuclei confers resistance to apoptosis and may explain the well-known association of this enzyme with tumor cell survival and spreading.

Apoptosis↗
PubMed2005

Accuracy of intraocular pressure measurements in new zealand white rabbits.

PURPOSE: Rabbits are commonly used for the evaluation of drugs and surgery to lower intraocular pressure (IOP). The accuracy of intraocular pressure measurement is therefore critical in the analysis of data and subsequent extrapolation to humans. The purpose of this study was to establish the most reliable technique, from several currently available methods, of measuring IOP in New Zealand White rabbits. METHODS: The IOPs of 11 healthy New Zealand White rabbits were measured with a fluid-filled pressure transducer system that was connected to the anterior chamber of each animal so that the IOP could be varied by altering the height of a bottle of balanced salt solution. Intraocular pressures were recorded over a range of 50 to 0 mm Hg by the transducer system, and comparative measurements at the same pressures were performed with the Tonopen XL (Mentor, Norwell, MA), the Perkins handheld applanation tonometer (Clement Clarke, Harlow, UK), and the Ocular Blood Flow (OBF) pneumatonometer (OBF Laboratories, Wiltshire, UK). RESULTS: All three tonometers underestimated the true IOP, especially at higher pressures. Although the mean difference in actual and tonometric IOP was least in the Tonopen XL, there was a high degree of variability through the entire range of IOPs measured. The Perkins tonometer, although slightly less accurate than the Tonopen XL, was more consistent in measurement. The OBF pneumatonometer was the least-reliable estimate of IOP. CONCLUSIONS: All tonometers underestimate IOP, with increasing inaccuracy at higher pressures. The Perkins applanation tonometer was the most reliable for measuring IOP in the range of 0 to 50 mm Hg in New Zealand White rabbits.

Animals↗
PubMed2005

Prolonged antiscarring effects of ilomastat and MMC after experimental glaucoma filtration surgery.

PURPOSE: To determine the long-term antiscarring effect of ilomastat treatment after experimental glaucoma filtration surgery (GFS). METHODS: In a randomized, prospective, masked-observer study, 21 New Zealand White rabbits underwent modified GFS. The animals were allocated to receive either intraoperative mitomycin-C (MMC) at a concentration of 0.2 mg/mL or postoperative subconjunctival injections of either ilomastat or phosphate-buffered saline (PBS). Fifteen injections were given to each animal during the study period. The animals were killed 60 days after surgery. Bleb morphology and intraocular pressures were recorded. Tissue sections were immunohistochemically stained for signs of scarring. RESULTS: Ilomastat significantly improved surgical outcome compared with vehicle (P < 0.0163) and length of bleb survival was similar to the MMC group. The mean day of failure was 46.2 (range, 42-60) with ilomastat, 51.3 (range, 49-60) with MMC, and 16 (range, 15-21) with vehicle. IOP maintenance with ilomastat was similar to that in the MMC group. Histologically, minimal scar tissue was seen with MMC and ilomastat. MMC-treated tissue demonstrated subconjunctival hypocellularity associated with peripheral fibrosis. Ilomastat resulted in normal-appearing conjunctival morphology. CONCLUSIONS: Ilomastat successfully prolongs bleb survival. MMP inhibition may provide an additional, potentially safer method of controlling intraocular pressure, thus preventing failure of glaucoma surgery, and may also act as a potential adjuvant treatment when MMC alone is inadequate.

Animals↗
PubMed2004

Needle revision of failing and failed trabeculectomy blebs with adjunctive 5-fluorouracil: survival analysis.

PURPOSE: To report the outcome of 5-fluorouracil (5-FU)-augmented bleb needling revision of failed and failing filtration blebs and to identify risk factors for failure, indicators for success, and any complications of the procedure. DESIGN: Prospective, observational, noncomparative, interventional case series with survival analysis. METHODS: The results of 101 bleb needling procedures augmented with subconjunctival 5-FU injection were determined after a minimum follow-up of 9 months. Kaplan-Meier plots were constructed and a Cox proportional hazards regression analysis was performed to assess the association between study factors and time to failure. MAIN OUTCOME MEASURES: Reduction in intraocular pressure (IOP) by 2 criteria (<22 mmHg, >30%), glaucoma medications, complications, and factors associated with outcome. RESULTS: At the time of their last follow-up visit, 60 eyes had an IOP <22 mmHg, mean IOP being reduced from 26.5 mmHg to 15 mmHg [corrected] after a median of 1 needling procedure (mean, 1.6). The median interval between the "index" filtration surgery and the first (or only) needling procedure was 3.1 months, with a range of 10 days to 11 years. There was a reduction in mean number of topical antiglaucoma agents from 0.7 to 0.2 per successful eye and a median follow-up duration of 18.7 months (range, 9.3-52.8 months [corrected]). Thus, the overall cross-sectional success rate of the procedure at the time of the last visit was 59.4%. Strong evidence was found for an association between the immediate attainment of a low IOP (<11 mmHg) and longer survival times. None of the other proposed factors that may have affected outcome were identified as having a statistically significant effect; however, this may have been the result of the low statistical power for some of the factors in this study. CONCLUSIONS: These data suggest that bleb needling augmented with 5-FU is a safe and effective method by which a significant number of failed or failing filtration blebs can be rescued from failure. Attaining an immediate reduction in IOP to <11 mmHg seems to be a favorable factor with respect to reasonably long-term efficacy .

Adult↗
PubMed2004

Flap and suture manipulation after trabeculectomy with adjustable sutures: titration of flow and intraocular pressure in guarded filtration surgery.

PURPOSE: To describe the intraocular pressure (IOP) changes resulting from scleral flap suture and scleral flap manipulation in an experimental model of conventional guarded filtration surgery. DESIGN: Experimental study. METHODS: Trabeculectomy operations were performed with adjustable sutures on 5 donor human eyes connected to a constant flow infusion and a real-time IOP monitoring system. Three different manipulations: posterior lip massage, suture adjustment using special forceps, and suture release, were tested on the completed operation site. MAIN OUTCOME MEASURES: The success in lowering IOP to the target range of 7 to 15 mm Hg within 5 interventions, the time to reach equilibrium IOP, and the frequency of undesired outcomes. RESULTS: Posterior lip massage, suture release, and suture adjustment lowered the IOP after stabilization to the target range in less than 5 interventions in 9%, 14%, and 100% respectively (P < 0.001). The median time for IOP to stabilize at the new level after each intervention after correction for the flow rates used was 36.3 minutes for massage, 8.5 minutes for releasable sutures, and 3.7 minutes for adjustment of sutures (P < 0.001). CONCLUSIONS: These results suggest that suture adjustment may be superior to both posterior lip massage and releasable sutures for managing IOP in the early phase following glaucoma surgery. Following clinical interventions that result in loss of anterior chamber volume, IOP checks should be made at least 40 minutes post-intervention or at a later time afterwards if there is a clinical risk of low aqueous production. Manipulation of the scleral flap and associated sutures may only lower the IOP for minutes to hours if the suture tension is not decreased.

Equipment Design↗
PubMed2004

Involvement of CTGF in TGF-beta1-stimulation of myofibroblast differentiation and collagen matrix contraction in the presence of mechanical stress.

PURPOSE: This study was undertaken to investigate the role of connective tissue growth factor (CTGF) in fibroblast-to-myofibroblast differentiation and fibroblast-mediated collagen matrix contraction in the presence of mechanical stress. METHODS: An in vitro three-dimensional contraction model of human corneal-fibroblast-seeded collagen lattices (FSCLs) in the presence of mechanical stress generated by attaching the lattices to the culture well was used to measure FSCL contraction. FSCLs were treated with CTGF; TGF-beta1; serum-free (SF) control medium; or TGF-beta1 plus antisense oligodeoxynucleotides to CTGF; TGF-beta1 plus scrambled-sequence oligodeoxynucleotide to CTGF; or TGF-beta antibody. Expression of alpha-smooth muscle actin (alpha-SMA) by fibroblasts in FSCLs was detected by immunostaining and confocal microscopy, whereas ELISA was used for the fibroblasts cultured on plastic. The conditioned media were analyzed by ELISA for CTGF production. RESULTS: Exogenous CTGF stimulated significantly less collagen matrix contraction and myofibroblast differentiation than TGF-beta1, but similar to that stimulated by SF. TGF-beta1 stimulated fibroblasts to express CTGF. CTGF antisense oligodeoxynucleotide inhibited TGF-beta1-stimulated myofibroblast differentiation and FSCL contraction. Exogenous CTGF circumvented the inhibitory effects of CTGF antisense on FSCL contraction. TGF-beta antibody significantly inhibited FSCL contraction and myofibroblast differentiation under mechanical stress and SF control conditions. CONCLUSIONS: In the presence of mechanical stress, CTGF is necessary for TGF-beta1-stimulation of myofibroblast differentiation and subsequent collagen matrix contraction, but CTGF alone is not sufficient to induce myofibroblast differentiation and collagen matrix contraction. Thus, TGF-beta1 appears to regulate multiple genes that are essential for fibroblast-mediated contraction of stressed matrix, one of which is CTGF.

Actins↗
PubMed2003

Temporal and spatial expression of matrix metalloproteinases during wound healing of human corneal tissue.

Our understanding of MMP expression during corneal repair has previously relied upon animal models, isolated human biopsy specimens and cell culture studies. The aim of this study was to determine the temporal and spatial expression of matrix metalloproteinases following wounding of cultured human corneal tissue. Human corneas were cultured and cut into six pieces. The epithelium was removed with a corneal brush. The tissue was then re-cultured and tissue pieces were fixed up to 7 days post-wounding. Matrix metalloproteinases were detected by in situ hybridisation and immunohistochemistry. Intracellular laminin-5, a marker of migratory epithelial cells, was located immunohistologically. In the time scale studied tissue series from nine corneas achieved coverage of the stroma with epithelial cells and partial repair of damaged basement membrane, demonstrated by the Periodic acid-Schiff reaction and haematoxylin and eosin counter-staining. By day 3, migrating epithelial cells and stromal cells beneath the wounded area expressed collagenase-1 (MMP-1). Stromelysin-1 (MMP-3) was expressed only by fibroblast-like stromal cells. Stromelysin-2 (MMP-10) was detected in migrating epithelial cells and remained when the stroma was surrounded by a monolayer of epithelial cells. By day 7, development of multi-layered epithelium around the tissue coincided with cessation of MMP expression in both epithelial and stromal cells, except for MMP-9, which remained in epithelial basal cells. Tissue inhibitor of matrix metalloproteinase-1 was mainly associated with stromal cells and was reduced upon formation of a multi-layered epithelium. This study demonstrates matrix metalloproteinase expression in epithelial and fibroblast-like cells following wounding of human corneal tissue in culture where the cells remain in contact with their natural matrices.

Basement Membrane↗
PubMed2003

Mediation of transforming growth factor-beta(1)-stimulated matrix contraction by fibroblasts: a role for connective tissue growth factor in contractile scarring.

Excessive cell-mediated tissue contraction after injury can lead to morbid contractile scarring in the body. In the eye this can cause blindness because of posterior capsule opacification, proliferative vitroretinopathy, failure of glaucoma filtration surgery, and corneal haze. During repair, transforming growth factor (TGF)-beta and connective tissue growth factor (CTGF) genes are co-ordinately expressed. Although TGF-beta and CTGF stimulate new matrix deposition, their role and regulation during contractile scarring is unknown. In this study, an in vitro model of collagen matrix contraction culminating from tractional forces generated by fibroblasts showed that both TGF-beta(1) and CTGF-stimulated contraction. Using a specific anti-sense oligodeoxynucleotide to CTGF the procontractile activity of TGF-beta(1) was found to be mediated by CTGF. During contraction fibroblasts produced similar levels of matrix metalloproteinases (MMPs)-2 and -9 with TGF-beta(1) or CTGF and a modest increase in MMP-1 with CTGF only (indicated by zymography and enzyme-linked immunosorbent assay). The requirement of MMPs for contraction was demonstrated using a broad-spectrum synthetic inhibitor. This study demonstrates a new function for CTGF in mediating matrix contraction by fibroblasts involving MMPs and suggests a novel regulatory mechanism for TGF-beta-stimulated contraction. Inhibition of CTGF activity or gene transcription could be a suitable target for anti-scarring therapies.

Animals↗