Cornea - ARVO

ARVO 2013 Annual Meeting Abstracts by Scientific Section/Group - Corneapatients tended significantly to have keratoplasty done at 20-30 years,while female patients at more than 30 years of age.Conclusions: In this hospital-based KC study, the severity is highwith an early onset and more rapid progress to advanced stage at ayounger age. Female patients had more sever disease. These may berelated to genetic and / or environmental factors. The results haveimplications for KC screening in Saudi Arabia (and probably nearbyMiddle-Eastern countries), to improve early detection andmanagment.Commercial Relationships: Samar A. Al-Swailem, None; SamuelC. Yiu, None; Abdullah Al-Assiri, None; Nasira Asghar, None;Albaraa Al-Qassimi, NoneProgram Number: 5301 Poster Board Number: C0220Presentation Time: 2:45 PM - 4:30 PMIncreased expression of secreted frizzled-related protein-1(SFRP-1) and microtubule-associated protein light chain 3 (LC3)in keratoconusOmer Iqbal, George Fisher, Samir Vira, Daniel Kahn, Daneyal Syed,Jawed Fareed, Charles S. Bouchard. Ophthalmology, Loyola,Maywood, IL.Purpose: To study the expression of secreted frizzled-related protein-1 (SFRP-1) and Light Chain 3 (LC3), an autophagy marker, inkeratoconus and to determine the proteomic profile of normal andkeratoconic epithelial and stromal layers by ProteinChip® usingSELDI-TOF-MSMethods: Under an IRB approved protocol, surgically discarded andde-identified normal donor (n=10) and keratoconus corneas (n=10)were obtained. A segment of the cornea was fixed in formalin forimmunohistochemical staining. From the remaining cornea theendothelium-Descemets membrane was removed. The endotheliumfree cornea was soaked in prewarmed 20mM EDTA solution for 30minutes and forceps were used to strip the epithelial and the stromallayers. The samples were homogenized and the proteinconcentrations adjusted to 1mg/ml. The homogenates were analyzedusing SELDI-TOF-MS. The formalin fixed paraffin-embeddedcorneal samples were cut into sections and mounted on slides. SFRP-1 antibody and LC3 antibody were used to performimmunohistochemical staining.Results: The proteomic profile showed absence of peaks in the 20-150 kDa range in the keratoconic epithelium. However, there weredistinct peaks in keratoconus at 10.8, 12.7, 13.1, 14.6, and 15.8 kDawhich were absent in normal samples. High expressivity of SFRP-1and LC3 was observed in the keratoconus corneas. There alsoappeared to be a correlation between the expression of SFRP1 andLC3 in keratoconus tissues. Low expressivity of SFRP1 resulted inlow expressivity of LC3 while medium-high expressivity of SFRP1resulted in medium to high expressivity of LC3.Conclusions: Increased expression of SFRP-1 and LC3 was observedin Keratoconus cornea. Keratocyte autophagy associated withKeratoconus may play a role in the pathogenesis of Keratoconus.Commercial Relationships: Omer Iqbal, None; George Fisher,None; Samir Vira, None; Daniel Kahn, None; Daneyal Syed,None; Jawed Fareed, None; Charles S. Bouchard, NoneSupport: Illinois Society for the Prevention of BlindnessProgram Number: 5302 Poster Board Number: C0221Presentation Time: 2:45 PM - 4:30 PMIL1B promoter polymorphisms are associated with keratoconusin a Japanese populationTakenori Mikami 1, 2 , Akira Meguro 1 , Takeshi Teshigawara 2 , MasakiTakeuchi 1 , Misaki Ishioka 1, 3 , Miki Iwasaki 3 , Kazumi Fukagawa 3 ,Kenji Konomi 4 , Jun Shimazaki 4 , Nobuhisa Mizuki 1 . 1 Ophthalmologyand Visual Science, Yokohama City University Graduate School ofMedicine, Yokohama, Japan; 2 Yokosuka Chuoh Eye Clinic,Yokosuka, Japan; 3 Ryogoku Eye Clinic, Tokyo, Japan; 4 Departmentof Ophthalmology, Ichikawa General Hospital, Tokyo DentalCollege, Ichikawa, Japan.Purpose: Previous study reported that the polymorphisms ofinterleukin 1 alpha (IL1A) and IL1B gene regions were associatedwith keratoconus in a Korean population. In this study, weinvestigated whether the IL1A and IL1B polymorphisms areassociated with keratoconus in a Japanese population.Methods: One hundred and sixty-nine Japanese patients withkeratoconus and 390 Japanese healthy controls were recruited. Wegenotyped one IL1A single-nucleotide polymorphism (SNP)(rs2071376) and two IL1B SNPs (rs1143627 and rs16944), and thefrequencies of alleles, genotypes, and haplotypes were comparedbetween cases and controls.Results: The significant associations were observed for rs1143627 (-31 T>C) and rs16944 (-511 C>T) in the IL1B promoter region, andthe T allele of rs1143627 and the C allele of rs16944 had anincreased risk of keratoconus (P = 0.014, OR = 1.38 and P = 0.033,OR = 1.33, respectively). The TT genotype of rs1143627 wasassociated with an increased risk for keratoconus (P = 0.033, OR =1.52). The CC genotype of rs16944 also showed an increased risk forkeratoconus, but this did not reach statistical significance (P = 0.058,OR = 1.45). For rs2071376 in IL1A, there were no significantdifferences of allele and genotype frequencies between cases andcontrols. With regard to haplotypic diversity, the haplotype createdby the T allele of rs1143627 and the C allele of rs16944 had a 1.72-fold increased risk of keratoconus (P = 4.0 × 10-5).Conclusions: Our results replicate associations reported recently in aKorean population. This suggests that the IL1B gene play animportant role in the development of keratoconus through geneticpolymorphisms.Commercial Relationships: Takenori Mikami, None; AkiraMeguro, None; Takeshi Teshigawara, None; Masaki Takeuchi,None; Misaki Ishioka, None; Miki Iwasaki, None; KazumiFukagawa, None; Kenji Konomi, None; Jun Shimazaki, SantenPharmaceutical Co. (F), Otsuka Pharmaceutical Co. (F), AbottMedical Optics (F); Nobuhisa Mizuki, NoneSupport: None in the SupportProgram Number: 5303 Poster Board Number: C0222Presentation Time: 2:45 PM - 4:30 PMKeratoconus Gene Mapping: Candidate Genes in the 14q11.2homozygous regionGovindasamy Kumaramanickavel 1 , Venkata Ramana Anandula 1 ,Vedam Ramprasad 3 , Nalla Thambi Jeyabalan 1 , Arkasubhra Ghosh 1 ,Rohit Shetty 2 . 1 Basic Science Research, Narayana Nethralaya,Bangalore, India; 2 Cornea, Narayana Nethralaya, Bangalore, India;3 Spinco-Biotech, Chennai, India.Purpose: Keratoconus (KC) is the most common corneal dystrophywith a prevalence rate of 0.05% of people in the USA, even though itis classified under rare diseases. Indian subcontinent has a four foldgreater incidence of the disease. The precise etiopathogenesis of KCis unclear. However, strong family history and large autosomaldominant and few recessive pedigrees' linkage with the disorder hasshown that genetics is one of the leading causes for KC. This study isto map the gene that is causative of the disease in a consanguineousautosomal recessive family.Methods: The family members underwent detailed ophthalmicevaluation including corneal topography. The members of theconsanguineous family were bled for DNA with all ethicalconsiderations. The samples were run on genomewide Affymetrix©2013, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permissionto reproduce any abstract, contact the ARVO Office at arvo@arvo.org.