collagen type xi

Summary

Summary: A fibrillar collagen found primarily in interstitial CARTILAGE. Collagen type XI is heterotrimer containing alpha1(XI), alpha2(XI) and alpha3(XI) subunits.

Top Publications

  1. Akawi N, al Gazali L, Ali B. Clinical and molecular analysis of UAE fibrochondrogenesis patients expands the phenotype and reveals two COL11A1 homozygous null mutations. Clin Genet. 2012;82:147-56 pubmed publisher
    ..In conclusion, our data shall improve the overall understanding of fibrochondrogenesis especially in surviving homozygous patients and, at least partly, explain the phenotypic variability associated with COL11A1 gene mutations. ..
  2. Goto T, Matsui Y, Fernandes R, Hanson D, Kubo T, Yukata K, et al. Sp1 family of transcription factors regulates the human alpha2 (XI) collagen gene (COL11A2) in Saos-2 osteoblastic cells. J Bone Miner Res. 2006;21:661-73 pubmed
    ..The results establish that Sp1 proteins regulate COL11A2 transcription by binding to its proximal promoter and directly interacting with CBP, p300, and HDAC. ..
  3. Acke F, Dhooge I, Malfait F, De Leenheer E. Hearing impairment in Stickler syndrome: a systematic review. Orphanet J Rare Dis. 2012;7:84 pubmed publisher
    ..Regular auditory follow-up is strongly advised, particularly because many Stickler patients are visually impaired. ..
  4. Masaki K, Gu J, Ghaffari R, Chan G, Smith R, Freeman D, et al. Col11a2 deletion reveals the molecular basis for tectorial membrane mechanical anisotropy. Biophys J. 2009;96:4717-24 pubmed publisher
    ..This anisotropy can be attributed to increased mechanical coupling provided by the collagen fibrils. Mechanisms by which changes in TM material properties may contribute to the threshold elevation in Col11a2 -/- mice are discussed...
  5. Mio F, Chiba K, Hirose Y, Kawaguchi Y, Mikami Y, Oya T, et al. A functional polymorphism in COL11A1, which encodes the alpha 1 chain of type XI collagen, is associated with susceptibility to lumbar disc herniation. Am J Hum Genet. 2007;81:1271-7 pubmed
    ..These observations indicate that type XI collagen is critical for IVD metabolism and that its decrease is related to LDH. ..
  6. Bowen K, Reimers A, Luman S, Kronz J, Fyffe W, Oxford J. Immunohistochemical localization of collagen type XI alpha1 and alpha2 chains in human colon tissue. J Histochem Cytochem. 2008;56:275-83 pubmed
    ..Although the function of collagen XI in the colon is unknown, our immunohistochemical characterization provides the foundation for future immunohistopathology studies of the colon. ..
  7. Warner L, Brown R, Yingst S, Oxford J. Isoform-specific heparan sulfate binding within the amino-terminal noncollagenous domain of collagen alpha1(XI). J Biol Chem. 2006;281:39507-16 pubmed
    b>Collagen type XI is a constituent of the pericellular matrix of chondrocytes and plays a role in the regulation of fibrillogenesis...
  8. Avcin T, Makitie O, Susic M, Miller S, Thorne C, Tenenbaum J, et al. Early-onset osteoarthritis due to otospondylomegaepiphyseal dysplasia in a family with a novel splicing mutation of the COL11A2 gene. J Rheumatol. 2008;35:920-6 pubmed
    ..Early-onset polyarticular OA may occur in adults without a known or obvious underlying skeletal dysplasia. This study provides an approach to the diagnosis of an underlying skeletal dysplasia in such individuals. ..
  9. Zhao Y, Zhou T, Li A, Yao H, He F, Wang L, et al. A potential role of collagens expression in distinguishing between premalignant and malignant lesions in stomach. Anat Rec (Hoboken). 2009;292:692-700 pubmed publisher

More Information

Publications62

  1. Chen W, Kahrizi K, Meyer N, Riazalhosseini Y, Van Camp G, Najmabadi H, et al. Mutation of COL11A2 causes autosomal recessive non-syndromic hearing loss at the DFNB53 locus. J Med Genet. 2005;42:e61 pubmed
    Allele variants of COL11A2, encoding collagen type XI alpha2, cause autosomal dominant non-syndromic hearing loss (ARNSHL) at the DFNA13 locus (MIM 601868) and various syndromes that include a deafness phenotype...
  2. Kim H, Watkinson J, Varadan V, Anastassiou D. Multi-cancer computational analysis reveals invasion-associated variant of desmoplastic reaction involving INHBA, THBS2 and COL11A1. BMC Med Genomics. 2010;3:51 pubmed publisher
  3. Majava M, Hoornaert K, Bartholdi D, Bouma M, Bouman K, Carrera M, et al. A report on 10 new patients with heterozygous mutations in the COL11A1 gene and a review of genotype-phenotype correlations in type XI collagenopathies. Am J Med Genet A. 2007;143A:258-64 pubmed
    ..The remaining 6/10 patients had an overlapping Marshall-Stickler phenotype with less pronounced facial features. None of these had a mutation in the hot spot region of intron 50. ..
  4. van Beelen E, Leijendeckers J, Huygen P, Admiraal R, Hoefsloot L, Lichtenbelt K, et al. Audiometric characteristics of two Dutch families with non-ocular Stickler syndrome (COL11A2). Hear Res. 2012;291:15-23 pubmed publisher
    ..Psychophysical measurements in non-ocular Stickler patients were suggestive of intra-cochlear conductive hearing impairment. ..
  5. Richards A, McNinch A, Whittaker J, Treacy B, Oakhill K, Poulson A, et al. Splicing analysis of unclassified variants in COL2A1 and COL11A1 identifies deep intronic pathogenic mutations. Eur J Hum Genet. 2012;20:552-8 pubmed publisher
    ..Another variant produces transcripts that result in either haploinsufficiency or a dominant negative effect, potentially modifying the disease phenotype. ..
  6. Fischer H, Salahshor S, Stenling R, Bjork J, Lindmark G, Iselius L, et al. COL11A1 in FAP polyps and in sporadic colorectal tumors. BMC Cancer. 2001;1:17 pubmed
    ..Our results suggest that expression of COL11A1 in colorectal tumors could be associated with the APC/beta-catenin pathway in FAP and sporadic colorectal cancer. ..
  7. De Leenheer E, McGuirt W, Kunst H, Huygen P, Smith R, Cremers C. The phenotype of DFNA13/COL11A2. Adv Otorhinolaryngol. 2002;61:85-91 pubmed
  8. Tompson S, Faqeih E, Ala Kokko L, Hecht J, Miki R, Funari T, et al. Dominant and recessive forms of fibrochondrogenesis resulting from mutations at a second locus, COL11A2. Am J Med Genet A. 2012;158A:309-14 pubmed publisher
    ..These findings thus demonstrate that fibrochondrogenesis can result from either recessively or dominantly inherited mutations in COL11A2...
  9. Goldstein O, Guyon R, KUKEKOVA A, Kuznetsova T, Pearce Kelling S, Johnson J, et al. COL9A2 and COL9A3 mutations in canine autosomal recessive oculoskeletal dysplasia. Mamm Genome. 2010;21:398-408 pubmed publisher
  10. Carter E, Raggio C. Genetic and orthopedic aspects of collagen disorders. Curr Opin Pediatr. 2009;21:46-54 pubmed
    ..Findings range from lethal to mild, depending on the mutation of the collagen gene and its subsequent effect on the structure and/or metabolism of the resultant procollagen and/or collagen protein and its function in the body. ..
  11. Halsted K, Bowen K, Bond L, Luman S, Jorcyk C, Fyffe W, et al. Collagen alpha1(XI) in normal and malignant breast tissue. Mod Pathol. 2008;21:1246-54 pubmed publisher
    ..Collagen alpha1(XI) appears to be downregulated in stroma surrounding breast cancer. Detection of collagen XI in breast tissue may help predict women who have lymph node metastases. ..
  12. Vuoristo M, Pappas J, Jansen V, Ala Kokko L. A stop codon mutation in COL11A2 induces exon skipping and leads to non-ocular Stickler syndrome. Am J Med Genet A. 2004;130A:160-4 pubmed
    ..This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148-7299/suppmat/index.html. ..
  13. Tompson S, Bacino C, Safina N, Bober M, Proud V, Funari T, et al. Fibrochondrogenesis results from mutations in the COL11A1 type XI collagen gene. Am J Hum Genet. 2010;87:708-12 pubmed publisher
    ..These findings identify COL11A1 as a locus for fibrochondrogenesis and indicate that there might be phenotypic manifestations among carriers. ..
  14. Shpargel K, Makishima T, Griffith A. Col11a1 and Col11a2 mRNA expression in the developing mouse cochlea: implications for the correlation of hearing loss phenotype with mutant type XI collagen genotype. Acta Otolaryngol. 2004;124:242-8 pubmed
    ..The expression patterns suggest essential roles for Col11a1 and Col11a2 in the basilar or tectorial membranes. ..
  15. Admiraal R, Szymko Y, Griffith A, Brunner H, Huygen P. Hearing impairment in Stickler syndrome. Adv Otorhinolaryngol. 2002;61:216-23 pubmed
  16. Kubo T, Matsui Y, Goto T, Yukata K, Yasui N. Overexpression of HMGA2-LPP fusion transcripts promotes expression of the alpha 2 type XI collagen gene. Biochem Biophys Res Commun. 2006;340:476-81 pubmed
    ..These results indicate that in vivo overexpression of HMGA2-LPP promotes chondrogenesis by upregulating cartilage-specific collagen gene expression through the N-terminal DNA binding domains. ..
  17. Richards A, McNinch A, Martin H, Oakhill K, Rai H, Waller S, et al. Stickler syndrome and the vitreous phenotype: mutations in COL2A1 and COL11A1. Hum Mutat. 2010;31:E1461-71 pubmed publisher
    ..We have identified 57 novel mutations including missense changes in both COL2A1 and COL11A1 and have also detected two cases of complete COL2A1 gene deletions using MLPA...
  18. Poulson A, Hooymans J, Richards A, Bearcroft P, Murthy R, Baguley D, et al. Clinical features of type 2 Stickler syndrome. J Med Genet. 2004;41:e107 pubmed
  19. Anastassiou D, Rumjantseva V, Cheng W, Huang J, Canoll P, Yamashiro D, et al. Human cancer cells express Slug-based epithelial-mesenchymal transition gene expression signature obtained in vivo. BMC Cancer. 2011;11:529 pubmed publisher
  20. Chong I, Chang M, Chang H, Yu Y, Sheu C, Tsai J, et al. Great potential of a panel of multiple hMTH1, SPD, ITGA11 and COL11A1 markers for diagnosis of patients with non-small cell lung cancer. Oncol Rep. 2006;16:981-8 pubmed
    ..binding protein 2 (HABP2), Crystalline-mu (CRYM), Ceruloplasmin (CP), Integrin alpha-11 subunit (ITGA11), Collagen type XI alpha I (COL11A1), and Lung-specific X protein (Lun X)...
  21. Snead M, McNinch A, Poulson A, Bearcroft P, Silverman B, Gomersall P, et al. Stickler syndrome, ocular-only variants and a key diagnostic role for the ophthalmologist. Eye (Lond). 2011;25:1389-400 pubmed publisher
    ..We highlight the recently identified subgroups with a high risk of retinal detachment but with minimal or absent systemic involvement--a particularly important group for the ophthalmologist to identify...
  22. Van Camp G, Snoeckx R, Hilgert N, van den Ende J, Fukuoka H, Wagatsuma M, et al. A new autosomal recessive form of Stickler syndrome is caused by a mutation in the COL9A1 gene. Am J Hum Genet. 2006;79:449-57 pubmed
    ..Mutation analysis of this gene is recommended in patients with Stickler syndrome with possible autosomal recessive inheritance. ..
  23. Park K, Kang E, Jeon Y, Kim N, Kim N, Yoo H, et al. Identification of novel regulators of apoptosis using a high-throughput cell-based screen. Mol Cells. 2007;23:170-4 pubmed
    ..We conclude that a subcellular image-based apoptotic screen is useful for identifying genes with proapoptotic activity. ..
  24. Csordas A, Wick G, Bernhard D. Hydrogen peroxide-mediated necrosis induction in HUVECs is associated with an atypical pattern of caspase-3 cleavage. Exp Cell Res. 2006;312:1753-64 pubmed
    ..Thus, the pattern of caspase-3 cleavage might reflect the proteolytic system engaged in the cell death machinery in HUVECs. ..
  25. Xu F, Li H, Zhao C, Liang Z, Huang M, Li Q, et al. Characterization of Chondrogenic Gene Expression and Cartilage Phenotype Differentiation in Human Breast Adipose-Derived Stem Cells Promoted by Ginsenoside Rg1 In Vitro. Cell Physiol Biochem. 2015;37:1890-902 pubmed publisher
    ..Two weeks after induction, the expression of chondrogenic genes (collagen type II, collagen type XI, ACP, COMP and ELASTIN) was determined using real-time PCR in all groups...
  26. Merritt T, Bick R, Poindexter B, Alcorn J, Hecht J. Unique matrix structure in the rough endoplasmic reticulum cisternae of pseudoachondroplasia chondrocytes. Am J Pathol. 2007;170:293-300 pubmed
    ..Altogether, these data suggest that mutant COMP initiates and perhaps catalyzes premature intracellular matrix assembly...
  27. Lee H, Zhu X, Zhu X, Skidmore S, Perry G, Sayre L, et al. The essential role of ERK in 4-oxo-2-nonenal-mediated cytotoxicity in SH-SY5Y human neuroblastoma cells. J Neurochem. 2009;108:1434-41 pubmed publisher
    ..Overall, these data strongly suggest that ERK plays an essential role in ONE-mediated cytotoxicity and that ERK is an upstream component of p53-mediated apoptosis. ..
  28. Frischknecht M, Niehof Oellers H, Jagannathan V, Owczarek Lipska M, Drogemuller C, Dietschi E, et al. A COL11A2 mutation in Labrador retrievers with mild disproportionate dwarfism. PLoS ONE. 2013;8:e60149 pubmed publisher
    ..The identification of this candidate causative mutation thus widens the known phenotypic spectrum of COL11A2 mutations. We speculate that non-pathogenic COL11A2 variants might even contribute to the heritable variation in height...
  29. Chen Y, Chen S, Ho P, Lin C, Cheng Y, Wang J, et al. Apoptosis of T-leukemia and B-myeloma cancer cells induced by hyperbaric oxygen increased phosphorylation of p38 MAPK. Leuk Res. 2007;31:805-15 pubmed
    ..HBO(2) treatment leads to caspase-3, caspase-7 activation and further cleavage of PARP within cells. Furthermore, the increased phosphorylation of p38 MAPK was demonstrated in both Jurkat and NCI-H929 cells. ..
  30. Chen H, Jia W, Xu X, Fan Y, Zhu D, Wu H, et al. Upregulation of PEDF expression by PARP inhibition contributes to the decrease in hyperglycemia-induced apoptosis in HUVECs. Biochem Biophys Res Commun. 2008;369:718-24 pubmed publisher
    ..These results give the first direct demonstration that PEDF might represent a target for PARP inhibition treatment and the effects of PEDF on endothelial cells growth are context dependent. ..
  31. Onyango I, Tuttle J, Bennett J. Activation of p38 and N-acetylcysteine-sensitive c-Jun NH2-terminal kinase signaling cascades is required for induction of apoptosis in Parkinson's disease cybrids. Mol Cell Neurosci. 2005;28:452-61 pubmed
    ..PD mitochondrial genes expressed in cybrids stimulate pro-apoptotic cell signaling and biochemistry through oxidative stress. These results support development of antioxidative therapeutics for PD. ..
  32. Xu L, Peng H, Wu D, Hu K, Goldring M, Olsen B, et al. Activation of the discoidin domain receptor 2 induces expression of matrix metalloproteinase 13 associated with osteoarthritis in mice. J Biol Chem. 2005;280:548-55 pubmed
    ..The specific induction of MMP-13 by DDR2 in response to its cartilage-specific ligand, type II collagen, may contribute to cartilage damage in hereditary OA. ..
  33. Masago Y, Hosoya A, Kawasaki K, Kawano S, Nasu A, Toguchida J, et al. The molecular chaperone Hsp47 is essential for cartilage and endochondral bone formation. J Cell Sci. 2012;125:1118-28 pubmed publisher
    ..These results demonstrate that Hsp47 is indispensable for well-organized cartilage and normal endochondral bone formation. ..
  34. Hsu C, Lin Y, Chou C, Zhou S, Hsu Y, Liu C, et al. Mechanisms of grape seed procyanidin-induced apoptosis in colorectal carcinoma cells. Anticancer Res. 2009;29:283-9 pubmed
    ..GSP inhibited the proliferation of some colorectal carcinoma cell lines and was associated with an apoptotic mechanism involving a loss of mitochondrial membrane potential and caspase-3 activation in these cells. ..
  35. Virtanen I, Karppinen J, Taimela S, Ott J, Barral S, Kaikkonen K, et al. Occupational and genetic risk factors associated with intervertebral disc disease. Spine (Phila Pa 1976). 2007;32:1129-34 pubmed
    ..Of the independent genetic markers, IL1A -889T allele had strongest association with IDD-phenotype. ..
  36. Pappano W, Steiglitz B, Scott I, Keene D, Greenspan D. Use of Bmp1/Tll1 doubly homozygous null mice and proteomics to identify and validate in vivo substrates of bone morphogenetic protein 1/tolloid-like metalloproteinases. Mol Cell Biol. 2003;23:4428-38 pubmed
    ..Removal of functional redundancy also enabled use of Bmp1(-/-) Tll1(-/-) cells in a proteomics approach for identifying novel substrates of Bmp1 and Tll1 products. ..
  37. Curry J, Angove H, Fazal L, Lyons J, Reule M, Thompson N, et al. Aurora B kinase inhibition in mitosis: strategies for optimising the use of aurora kinase inhibitors such as AT9283. Cell Cycle. 2009;8:1921-9 pubmed
    ..These findings have implications for optimizing the efficacy of Aurora kinase inhibitors in clinical practice. ..
  38. Nikopensius T, Jagomagi T, Krjutskov K, Tammekivi V, Saag M, Prane I, et al. Genetic variants in COL2A1, COL11A2, and IRF6 contribute risk to nonsyndromic cleft palate. Birth Defects Res A Clin Mol Teratol. 2010;88:748-56 pubmed publisher
    ..It is likely that variation in cartilage collagen II and XI genes, IRF6, and the Wnt and FGF signaling pathway genes contributes susceptibility to nonsyndromic cleft palate in Northeastern European populations. ..
  39. Suzuki K, Matsui Y, Higashimoto M, Kawaguchi Y, Seki S, Motomura H, et al. Myxoid liposarcoma-associated EWSR1-DDIT3 selectively represses osteoblastic and chondrocytic transcription in multipotent mesenchymal cells. PLoS ONE. 2012;7:e36682 pubmed publisher
    ..A better understanding of this process is fundamental to the elucidation of possible direct lineage reprogramming in oncogenic sarcoma transformation mediated by fusion proteins. ..
  40. Zhao W, Kridel S, Thorburn A, Kooshki M, Little J, Hebbar S, et al. Fatty acid synthase: a novel target for antiglioma therapy. Br J Cancer. 2006;95:869-78 pubmed
    ..Finally, RNAi-mediated knockdown of FAS leading to reduced FAS enzymatic activity was associated with decreased glioma cell viability. These findings suggest that FAS might be a novel target for antiglioma therapy...
  41. Jakkula E, Melkoniemi M, Kiviranta I, Lohiniva J, Räinä S, Perala M, et al. The role of sequence variations within the genes encoding collagen II, IX and XI in non-syndromic, early-onset osteoarthritis. Osteoarthritis Cartilage. 2005;13:497-507 pubmed
    ..It is also possible that some OA cases represent the mild end of the chondrodysplasia phenotypic spectrum. The major susceptibility alleles in this form of OA, however, remain to be identified. ..
  42. Vargas A, McCart Reed A, Waddell N, Lane A, Reid L, Smart C, et al. Gene expression profiling of tumour epithelial and stromal compartments during breast cancer progression. Breast Cancer Res Treat. 2012;135:153-65 pubmed publisher
    ..We propose that these expression changes could be involved in facilitating the transition from in situ disease to invasive cancer and may thus mark a critical point in disease development. ..
  43. Minegishi Y, Hosokawa K, Tsumaki N. Time-lapse observation of the dedifferentiation process in mouse chondrocytes using chondrocyte-specific reporters. Osteoarthritis Cartilage. 2013;21:1968-75 pubmed publisher
    ..Chondrocyte dedifferentiation does not appear to be associated with cell division. ..
  44. Bhattacharyya S, Borthakur A, Dudeja P, Tobacman J. Carrageenan induces cell cycle arrest in human intestinal epithelial cells in vitro. J Nutr. 2008;138:469-75 pubmed
    ..These data document for the first time, to our knowledge, marked adverse effects of low concentrations of CGN on survival of normal human IEC and suggest that CGN exposure may have a role in development of human intestinal pathology. ..
  45. Oh H, Kido T, Lau Y. PIAS1 interacts with and represses SOX9 transactivation activity. Mol Reprod Dev. 2007;74:1446-55 pubmed
    ..Thus, PIAS1 appears to repress SOX9 activity by at least two SUMO-ligase dependent mechanisms: (1) the SUMOylation of SOX9 and (2) SUMOylation of unknown factors associated with SOX9 and/or PIAS1. ..
  46. Murai J, Ikegami D, Okamoto M, Yoshikawa H, Tsumaki N. Insulation of the ubiquitous Rxrb promoter from the cartilage-specific adjacent gene, Col11a2. J Biol Chem. 2008;283:27677-87 pubmed publisher
    ..Our results showed that the intergenic sequence including 11P insulates Rxrb promoter from Col11a2 enhancer, possibly associating with unknown factors that recognize a motif similar to CTCF. ..
  47. Goessler U, Bugert P, Bieback K, Sadick H, Baisch A, Hormann K, et al. In vitro analysis of differential expression of collagens, integrins, and growth factors in cultured human chondrocytes. Otolaryngol Head Neck Surg. 2006;134:510-5 pubmed
    ..TGF-beta3 and -beta4 might influence the dedifferentiation, which is fortified by the expression of TGF-beta receptor III. Integrin beta1, beta5, and alpha5 might be involved in signal transmission for the dedifferentiation. ..
  48. Kitagawa A, Miura Y, Saura R, Mitani M, Ishikawa H, Hashiramoto A, et al. Anchorage on fibronectin via VLA-5 (alpha5beta1 integrin) protects rheumatoid synovial cells from Fas-induced apoptosis. Ann Rheum Dis. 2006;65:721-7 pubmed
    ..Anchorage of RA-FLS on matrix Fn via VLA-5 protects RA-FLS from Fas-induced apoptosis, and Fn abundantly present in rheumatoid synovium appears to afford RA-FLS resistance against apoptosis induction in vivo. ..
  49. Hay M, Patricios J, Collins R, Branfield A, Cook J, Handley C, et al. Association of type XI collagen genes with chronic Achilles tendinopathy in independent populations from South Africa and Australia. Br J Sports Med. 2013;47:569-74 pubmed publisher
  50. Lu S, Carlsen S, Hansson A, Holmdahl R. Immunization of rats with homologous type XI collagen leads to chronic and relapsing arthritis with different genetics and joint pathology than arthritis induced with homologous type II collagen. J Autoimmun. 2002;18:199-211 pubmed
    ..Taken together, C(XI)IA is a chronic relapsing and erosive polyarthritis that is MHC associated, which in fact fulfills the criteria for diagnosis of RA. Thus the C(XI)IA model will be useful as a novel and relevant animal model for RA...
  51. Cheung H, Lynn Kelly N, Liston P, Korneluk R. Involvement of caspase-2 and caspase-9 in endoplasmic reticulum stress-induced apoptosis: a role for the IAPs. Exp Cell Res. 2006;312:2347-57 pubmed
    ..However, among HIAP1, HIAP2 and XIAP, only HIAP2 binds and inhibits caspase-2. Our results thus indicate a novel mechanism by which HIAP2 can regulate ER-initiated apoptosis by modulating the activity of caspase-2. ..
  52. Outani H, Okada M, Yamashita A, Nakagawa K, Yoshikawa H, Tsumaki N. Direct induction of chondrogenic cells from human dermal fibroblast culture by defined factors. PLoS ONE. 2013;8:e77365 pubmed publisher
    ..The human iChon cells formed cartilage but not tumors in nude mice. This approach could lead to the preparation of cartilage directly from skin in human, without going through pluripotent stem cells. ..
  53. McLeod D, Black G, Bishop P. Vitreous phenotype: genotype correlation in Stickler syndrome. Graefes Arch Clin Exp Ophthalmol. 2002;240:63-5; author reply 66 pubmed