Biomedical subjects

Dennis Shun Chiu Lam

Publications and source records attributed to Dennis Shun Chiu Lam.

12 recordsLinked to original sources

PubMed2007

Regional variations in the relationship between macular thickness measurements and myopia.

PURPOSE: To investigate the relationship between myopia and macular thickness, as measured by optical coherence tomography. METHODS: A total of 143 normal subjects comprising 80 eyes with high myopia (spherical equivalent [SE] < -6.0 D), 37 eyes with low to moderate myopia (SE between -6.0 and -0.5 D), and 26 nonmyopic eyes (SE > -0.5 D) were analyzed in this cross-sectional study. Total average, foveal, and inner and outer average macular thicknesses measured by the StratusOCT (Carl Zeiss Meditec Inc., Dublin, CA) were compared among the three diagnostic groups. Associations between macular thickness and refractive error/axial length were evaluated by linear regression analysis. RESULTS: The minimum foveal and average foveal (1-mm ring on the OCT retinal thickness map) thicknesses were significantly greater, and the outer ring macular (3-6-mm) thicknesses significantly lower in the high myopic eyes than in the low to moderate myopic and nonmyopic eyes. No significant difference was found in the inner ring (1-3-mm) macular thickness measurements among the groups. There was a positive correlation between the axial length and the average foveal thickness (r = 0.374, P < 0.001). Negative correlations were found between axial length and the average outer ring macular thickness (r= -0.471, P < 0.001) and total average macular thickness (r= -0.311, P < 0.001). CONCLUSIONS: Retinal thickness is related to refractive error/axial length in normal subjects with regional variations in correlation within the 6-mm macular region. Analysis of macular thickness in the evaluation of macular diseases and glaucoma should be interpreted only in the context of refractive errors and the location of measurement.

Adult↗

PubMed2006

Measuring triamcinolone acetonide in aqueous humor by gas chromatography-electron-capture negative-ion mass spectrometry.

Intravitreal triamcinolone acetonide (IVTA) injection has been used in the treatment of various posterior segment diseases. One of the side effects of IVTA is raised intraocular pressure, which may be secondary to triamcinolone acetonide (TAA)'s effects on the trabecular meshwork that affects aqueous outflow. In order to study the biological effects of TAA on the trabecular meshwork, we firstly need to reliably and accurately detect the concentration of TAA in tissue cells or fluids. In this study we have described a technique of using gas chromatography-electron-capture-negative-ion mass spectrometry (GC-NCI-MS) to develop a simple, sensitive, selective and validated method to detect TAA in aqueous humor (AH) of rabbits following IVTA and subconjunctival TAA injections. We derivatized TAA from extracted aqueous sample by acetic anhydride and BSTFA, respectively, and analyzed by GC-NCI-MS. The detection limit was 0.3ng/ml, linearity over 0.995 from 0 to 300ng/ml. The reproducibility ranged from 10.4 to 3.9 for concentrations from 3 to 300ng/ml, and recovery was over 95% for the concentrations 10, 60, and 200ng/ml. No interference was found from 159 aqueous samples. There was no TAA residue carried to the next injection from previously high concentration injection, 10,000ng/ml. We have provided an alternative, rapid, and robust method other than LC-MS-MS for TAA detection in AH.

Animals↗

PubMed2006

A genome-wide scan maps a novel juvenile-onset primary open angle glaucoma locus to chromosome 5q.

PURPOSE: To map the disease-associated locus of a family with autosomal dominant juvenile-onset primary open angle glaucoma (JOAG) and to screen the novel glaucoma gene WD repeat domain 36 (WDR36). METHODS: Complete ophthalmic examination and genomic DNA were obtained from 27 family members, in which nine were confirmed JOAG patients. Myocilin (MYOC), optineurin (OPTN), and WDR36 were screened for mutations by polymerase chain reaction and direct sequencing. Genome-wide scanning was carried out using the ABI PRISM Linkage Mapping Set MD-10. Two-point and multipoint linkage analyses were performed with the MLINK, ILINK, and LINKMAP programs. For fine mapping, additional markers flanking the most promising region on chromosome 5q were also analyzed. The significance of LOD scores was tested with simulation analyses using FASTLINK. Haplotypes were constructed using Simwalk2. RESULTS: MYOC or OPTN mutations were excluded in all family members. A maximum LOD score value of 4.82 at theta=0.00 was obtained for the marker D5S2011. Markers D5S2065, D5S1384, D5S471, D5S503, D5S2098, and D5S638 had LOD score values over 4.0 at theta=0.00. Haplotype analysis and recombination mapping further confined this region to 5q22.1-q32 within a region of 36 Mb flanked by D5S2051 and D5S2090. Screening of the novel WDR36 glaucoma-associated gene, which lies centromeric to the disease interval, revealed no mutations within any of the 23 coding exons or splicing junctions. CONCLUSIONS: Our results provided the mapping of a novel locus for JOAG at 5q and excluded coding or splicing junctions mutations within the WDR36 gene.

Adolescent↗

PubMed2006

Molecular diagnostics of genetic eye diseases.

Eye diseases can be simple or complex, and mostly of heterogeneous molecular genetics. Some eye diseases are caused by mutations in a single gene, but some diseases, such as primary open angle glaucoma, can be due to sequence variations in multiple genes. In some diseases, both genetic and epigenetic mechanisms are involved, as was recently revealed in the mechanism of retinoblastoma. Disease causative mutations and phenotypes may vary by ethnicity and geography. To date, more than a hundred candidate genes for eye diseases are known, although less than 20 have definite disease-causing mutations. The three common genetic eye diseases, primary open angle glaucoma, age-related macular degeneration, and retinitis pigmentosa, all have known gene mutations, but these account for only a portion of the patients. While the search for eye disease genes and mutations still goes on, known mutations have been utilized for diagnosis. Genetic markers for pre-symptomatic and pre-natal diagnosis are available for specific diseases such as primary open angle glaucoma and retinoblastoma. This paper reviews the molecular basis of common genetic eye diseases and the available genetic markers for clinical diagnosis. Difficulties and challenges in molecular investigation of some eye diseases are discussed. Establishment of ethnic-specific disease databases that contain both clinical and genetic information for identification of genetic markers with diagnostic, prognostic, or pharmacological value is strongly advocated.

Eye Diseases, Hereditary↗

PubMed2006

Association of apolipoprotein E polymorphisms with normal tension glaucoma in a Chinese population.

PURPOSE: To evaluate the role of apolipoprotein E (APOE) polymorphisms in primary open angle glaucoma (POAG). METHODS: A cohort of 400 unrelated Chinese POAG patients was examined, including 294 cases of high tension glaucoma (HTG) and 106 with normal tension glaucoma (NTG). Also studied were 300 unrelated Chinese control subjects. The genotypes of the APOE polymorphisms in exon 4 and in the promoter at positions -491, -427, and -219 were determined by polymerase chain reaction and restriction endonuclease analysis. Frequencies of the genotypes were compared between patients and controls by chi test or Fisher exact test. The association of APOE polymorphisms with POAG phenotypes including age at diagnosis, intraocular pressure (IOP) at diagnosis, highest IOP, cup-disc ratio, and visual field score was investigated by the Kruskal-Wallis test. RESULTS: No significant difference was detected in the frequencies of APOE promoter polymorphisms between POAG patients and control subjects (P>0.0125). For the exon 4 polymorphism, when compared with control subjects, the frequency of epsilon 4 carriers was significantly lower in patients with NTG (P=0.008; odds ratio=0.36, 95% confidence interval=0.17, 0.79) but not in HTG (P=0.07). Compared with -219TT, the -219G carriers had a significant higher age at diagnosis (P=0.0046). No significant association was found between other APOE polymorphisms and POAG phenotypes (P>0.07). CONCLUSIONS: Our findings suggest that the APOE epsilon 4 allele confers a protective effect against NTG, whereas the APOE promoter polymorphisms do not contribute to POAG risk. However, the APOE -219G carriers tended to have later-onset POAG.

Adolescent↗

PubMed2006

Retinal nerve fiber layer measurements in myopia: An optical coherence tomography study.

PURPOSE: To evaluate the relationship between retinal nerve fiber layer (RNFL) thickness measured by optical coherence tomography (OCT) and the axial length/refractive error of the eye. METHODS: A total of 115 eyes of 115 healthy subjects, comprising 75 eyes with high myopia (spherical equivalent [SE] < -6.0 D) and 40 eyes with low to moderate myopia (SE between -6.0 D and -0.5D), were analyzed in this cross-sectional study. Total average and mean clock hour RNFL thicknesses were measured by OCT and compared between the two myopia groups. Associations between RNFL measurements and axial length and spherical equivalent were evaluated by linear regression analysis. RESULTS: The RNFL measurements were significantly lower in the high myopia group compared with those of the low-to-moderate myopia group at 12, 1, and 7 o'clock (right eye orientation). Apart from the temporal clock hours, significant correlations were evident between RNFL measurements and the axial length and spherical equivalent. The average RNFL thickness decreased with increasing axial length (r = -0.314, P = 0.001) and negative refractive power (r = 0.291, P = 0.002). A significant proportion of myopic eyes were classified as outside normal limits, with reference to the normative database. The most frequently abnormal sector was at 2 o'clock, where 16.5% of myopic eyes were outside normal limits. CONCLUSIONS: RNFL measurements vary with the axial length/refractive error of the eye. Analysis of RNFL thickness in the evaluation of glaucoma should always be interpreted with reference to the refractive status. Although the normative database provided by OCT has been helpful in identifying ocular diseases involving the RNFL, it may not be reliable in the analysis of myopic eyes.

Adult↗

PubMed2005

Gene mapping for primary open angle glaucoma.

Primary open angle glaucoma (POAG) is a leading cause of visual impairment and blindness worldwide. To date, at least 20 genetic loci for POAG have been reported. Only 3 causative genes are identified from these loci: myocilin (MYOC), optineurin (OPTN) and WD repeat domain 36 (WDR36), which together account for less than 10% of POAG. Only a portion of POAG follows Mendelian inheritance, and a considerable fraction results from a large number of variants in several genes, each contributing small effects. Over the past 10 years, there has been vigorous research on mapping the POAG genes. The main technological approaches are functional cloning, family linkage analysis, genome-wide scan, case-control association study, and microarray analysis. Association studies found 16 genes related to POAG, but reports on glaucoma-causing effects of these genes are conflicting. Ten microarray gene expression studies related to POAG have been published. A number of genes potentially related to POAG have been identified, and they provide a good resource to select candidate genes for mutation analysis in association studies. While linkage studies remain a mainstay, the current trend is to use genome-wide association studies to map genes for POAG. This review gives an overview of the efforts in the past decade to identify the POAG genes through linkage studies, genome-wide scans, case-control association studies and microarray studies. In the near future such comprehensive studies are expected to greatly advance our understanding of the genetic basis of POAG and provide information for effective glaucoma therapy.

Chromosome Mapping↗

PubMed2005

SNPs and interaction analyses of myocilin, optineurin, and apolipoprotein E in primary open angle glaucoma patients.

PURPOSE: To evaluate the association of myocilin (MYOC), optineurin (OPTN), and apolipoprotein E (APOE) genes and their interactions in primary open angle glaucoma (POAG). METHODS: A cohort of 400 unrelated POAG patients (294 high tension glaucoma, HTG, and 106 normal tension glaucoma, NTG) and 281 unrelated control subjects were recruited. All coding exons and splicing junctions in MYOC and OPTN were screened for sequence alterations. Common polymorphisms in APOE were genotyped. Single genes were investigated by univariate and haplotype analysis, and gene-gene interactions by logistic regression and stratified analysis. Multiple comparisons were corrected by the Bonferroni method. Bioinformatics analysis was performed to assess the conservation of mutation sites across species and to predict putative motifs and secondary structures in mutated proteins. RESULTS: Disease-causing mutations in MYOC and OPTN were identified in 1.75% and 1% of POAG patients, respectively. Most of these mutations were highly conserved across species, many predicted to create new motifs or change protein secondary structures. No individual MYOC polymorphisms significantly contributed to HTG or NTG. A haplotype containing the minor allele of the MYOC IVS2+35A>G increased NTG risk (p=0.0001). Three OPTN polymorphisms, T34T, IVS5+38T>G, and IVS8-53T>C increased NTG risk (p<0.0008), while IVS5+38T>G increased HTG risk (p=0.0006). One haplotype that contains the minor alleles of 3 OPTN polymorphisms, T34T, IVS5+38T>G, and IVS7+24G>A, increased NTG risk (p=0.0002). APOE epsilon4 carriers had a decreased NTG risk (p=0.007). Possible gene-gene interactions were found between MYOC, OPTN, and APOE. CONCLUSIONS: Disease-causing mutations in MYOC and OPTN accounted for only a small proportion of Chinese POAG patients. Common polymorphisms in MYOC, OPTN, and APOE might interactively contribute to POAG, indicating a polygenic etiology.

Adolescent↗

PubMed2003

Early pituitary-adrenal responses and retinopathy of prematurity in very low birth weight infants.

This longitudinal prospective study aimed to investigate the relationship between pituitary-adrenal responses and severity of retinopathy of prematurity (ROP) in 92 preterm, very low birth weight infants < or = 30 wk gestation. The human corticotropin releasing hormone stimulation test was performed on these infants at D 7 and 14 of postnatal life. Univariate analysis revealed significant associations between severity of ROP and gestational age (r = -0.53, p < 0.0001), birth weight (r = -0.56, p < 0.0001), Apgar score at 1 min (r = -0.27, p < 0.05), Clinical Risk Index for Babies score (r = 0.48, p < 0.0001), duration of mechanical ventilation (r = 0.48, p < 0.0001), oxygen dependency (r = 0.48, p < 0.0001), and length of hospitalization (r = 0.49, p < 0.0001). The stage of ROP was also significantly associated with the basal and peak plasma ACTH (r > -0.22, p < 0.05) and peak serum cortisol (r = -0.21, p = 0.05) at d 7. Multivariate analysis using the classification and regression trees indicated that the two most influential risk factors affecting the development of advanced stages of ROP (> or = stage 3) were i) birth weight and ii) oxygen dependency at 28 d of life or at 36 wk postconceptional age. Our findings suggest that early endogenous or stimulated pituitary-adrenal responses are not independent risk factors associated with the development of severe ROP. Low birth weight and prolonged oxygen exposure are likely to be important factors that influence the degree of damage inflicted on the retina.

Adrenocorticotropic Hormone↗

PubMed2003

The dual role of dexamethasone on anti-inflammation and outflow resistance demonstrated in cultured human trabecular meshwork cells.

PURPOSE: Dexamethasone (DEX) is a glucocorticoid commonly used in topical eyedrops to treat eye inflammation. It has an undesirable effect of inducing glaucoma in certain patients. In human Trabecular Meshwork (TM) cells DEX regulates a number of genes but its global influence on TM gene expression is still elusive. In the present work, DEX effects on global gene expressions of an established human TM cell line were studied by microarray. METHODS: The whole experiment of microarray was repeated three times. Differentially expressed genes were identified by an empirical Bayes approach and confirmed by Reverse Transcription Polymerase Chain Reaction. RESULTS: Eight genes (GAS1, CDH4, MT1L, CST3, ATF4, ASNS/TS11, CHOP, HSPA5) were identified that are at least a thousand times more likely to be differentially expressed due to DEX treatment and six genes (TSC22, LDHA, IGFBP2, TAGLN, SCG2, WARS) were identified that are at least a hundred times more likely to be differentially expressed due to DEX treatment. Except for MT1L, ASNS/TS11, IGFBP2, SCG2, and WARS, all the other genes are first reported here to be regulated by DEX in TM. Intriguingly, several of them have overlapping roles in anti-inflammatory response and outflow resistance. CONCLUSIONS: The results of our experiments on cultured human TM cells indicate that the increase in outflow resistance and ultimate ocular hypertension may be byproducts of the favorable anti-inflammatory response triggered by DEX.

Anti-Inflammatory Agents↗

PubMed2003

TGFbeta-induced factor: a candidate gene for high myopia.

PURPOSE: To investigate the coding exons of transforming growth factor (TGF)-beta-induced factor (TGIF) for mutations in Chinese patients with high myopia. METHODS: Seventy-one individuals with high myopia of -6.00 D or less and 105 control subjects were screened by DNA sequencing for sequence alterations. Univariate analysis and logistic regression were performed to identify single-nucleotide polymorphisms (SNPs) and their interactions in TGIF that may be associated with myopia. RESULTS: Six SNPs showed a significant difference (P < 0.05) between patient and control subject in univariate analysis. Four of them cause codon changes: G223R, G231S, P241T, and A262G. Among all the SNPs that entered multivariate analysis, only 657(T-->G) showed statistical significance in the logistic regression model (odds ratio 0.133; 95% confidence interval 0.037-0.488; P = 0.002). CONCLUSIONS: TGIF is a probable candidate gene for high myopia. Further studies are needed to identify the underlying mechanism.

Adult↗

PubMed2002

Differential occurrence of mutations causative of eye diseases in the Chinese population.

Ethnic differences and geographic variations affect the frequencies and nature of human mutations. In the literature, descriptions of causative mutations of eye diseases in the Chinese population are few. In this paper we attempt to reveal molecular information on genetic eye diseases involving Chinese patients from published and unpublished works by us and other groups. Our studies on candidate genes of eye diseases in the Chinese population in Hong Kong include MYOC and TISR for primary open angle glaucoma, RHO and RP1 for retinitis pigmentosa, ABCA4 and APOE for age-related macular degeneration, RB1 for retinoblastoma, APC for familial adenomatous polyposis with congenital hypertrophy of retinal pigment epithelium, BIGH3/TGFBI for corneal dystrophies, PAX6 for aniridia and Reiger syndrome, CRYAA and CRYBB2 for cataracts, and mtDNA for Leber hereditary optic neuropathy. We have revealed novel mutations in most of these genes, and in RHO, RP1, RB1, BIGH3, and PAX6 we have reported mutations that contribute to better understanding of the functions and properties of the respective gene products. We showed absence of MYOC does not necessarily cause glaucoma. No disease causative mutations have been identified in MYOC or ABCA4. There are similarities in the patterns of sequence alterations and phenotype-genotype associations in comparison with other ethnic groups, while the MYOC, RB1, APC, and PAX6 genes have more Chinese-specific sequence alterations. Establishment of a mutation database specific for the Chinese is essential for identification of genetic markers with diagnostic, prognostic, or pharmacological values.

Asian People↗