Seiji Takagi1,2,3, Michiko Mandai4,5,6, Yasuhiko Hirami4,5,6, Sunao Sugita4,5,6, Masayo Takahashi4,5,6, Yasuo Kurimoto4,5,6. 1. Department of Ophthalmology, Kobe City Eye Hospital, 2-1-8, Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan. tigerseiji@gmail.com. 2. Department of Ophthalmology, Kobe City Medical Center General Hospital, 2-2 Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan. tigerseiji@gmail.com. 3. Department of Ophthalmology, Toho University Ohashi Medical Center, 2-6-17 Ohashi, Meguro-ku, Tokyo, 153-8515, Japan. tigerseiji@gmail.com. 4. Department of Ophthalmology, Kobe City Eye Hospital, 2-1-8, Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan. 5. Department of Ophthalmology, Kobe City Medical Center General Hospital, 2-2 Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan. 6. Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
Abstract
PURPOSE: Stem cell therapy is a potential treatment for retinal disorders. We are currently exploring treating HLA matched patients of age-related macular degeneration (AMD) by using allogenic retinal pigment epithelium cells derived from induced pluripotent stem cells (iPS-RPE) from human leukocyte antigen (HLA) homozygote donors. The purpose of this study was to investigate the frequency of HLA class I and II alleles and haplotypes in Japanese patients with AMD. STUDY DESIGN: Cross-sectional observation clinical study. METHODS: A total of 138 consecutive patients diagnosed with neovascular AMD (mean age, 76.0 ± 7.8 years, 105 men) and 300 controls were included in the study. The frequencies of HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 alleles were determined using illumina MiSeq platform. Frequencies of HLA alleles at six loci in patients with AMD were compared with those of the controls. RESULTS: The alleles with the highest prevalence at each locus were A*24:02 (29.7%), B*52:01 (15.5%), C*12:02 (16.1%), DRB1*09:01 (19.1%), DQB1*06:01 (23.2%), and DPB1* 05:01 (40.5%). There were no significant associations between the HLA alleles and AMD. The most common haplotype was A*24:02-B*52:01-C*12:02-DRB1*15:02-DQB1*06:01-DPB1*09:01, with a 9.8% genetic frequency among all haplotypes, detected in 18.8% of the patients. CONCLUSION: The genotype of HLA in patients with AMD was not different from that in the Japanese control population. Thus, therapy with iPS-RPEof the most frequent HLA haplotype could be a feasible alternative for AMD in a wider population.
PURPOSE: Stem cell therapy is a potential treatment for retinal disorders. We are currently exploring treating HLA matched patients of age-related macular degeneration (AMD) by using allogenic retinal pigment epithelium cells derived from induced pluripotent stem cells (iPS-RPE) from human leukocyte antigen (HLA) homozygote donors. The purpose of this study was to investigate the frequency of HLA class I and II alleles and haplotypes in Japanese patients with AMD. STUDY DESIGN: Cross-sectional observation clinical study. METHODS: A total of 138 consecutive patients diagnosed with neovascular AMD (mean age, 76.0 ± 7.8 years, 105 men) and 300 controls were included in the study. The frequencies of HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 alleles were determined using illumina MiSeq platform. Frequencies of HLA alleles at six loci in patients with AMD were compared with those of the controls. RESULTS: The alleles with the highest prevalence at each locus were A*24:02 (29.7%), B*52:01 (15.5%), C*12:02 (16.1%), DRB1*09:01 (19.1%), DQB1*06:01 (23.2%), and DPB1* 05:01 (40.5%). There were no significant associations between the HLA alleles and AMD. The most common haplotype was A*24:02-B*52:01-C*12:02-DRB1*15:02-DQB1*06:01-DPB1*09:01, with a 9.8% genetic frequency among all haplotypes, detected in 18.8% of the patients. CONCLUSION: The genotype of HLA in patients with AMD was not different from that in the Japanese control population. Thus, therapy with iPS-RPEof the most frequent HLA haplotype could be a feasible alternative for AMD in a wider population.
Entities:
Keywords:
Age-related macular degeneration; Haplotype frequency; Human leukocyte antigen; Induced pluripotent stem cells; Japan
Authors: J A Thomson; J Itskovitz-Eldor; S S Shapiro; M A Waknitz; J J Swiergiel; V S Marshall; J M Jones Journal: Science Date: 1998-11-06 Impact factor: 47.728
Authors: Mandeep S Singh; Susanna S Park; Thomas A Albini; M Valeria Canto-Soler; Henry Klassen; Robert E MacLaren; Masayo Takahashi; Aaron Nagiel; Steven D Schwartz; Kapil Bharti Journal: Prog Retin Eye Res Date: 2019-09-05 Impact factor: 21.198