[Show abstract][Hide abstract] ABSTRACT: In an earlier study, a cDNA was cloned that showed abundant expression in the eye at postnatal day (P)2 but was downregulated at P10; it was named ODAG (ocular development-associated gene). Its biological function was examined by generating and analyzing transgenic mice overexpressing ODAG (ODAG Tg) in the eye and by identifying ODAG-binding proteins.
Transgenic mice were generated by using the mouse Crx promoter. EGFP was designed to be coexpressed with transgenic ODAG, to identify transgene-expressing cells. Overexpression of ODAG was confirmed by Northern and Western blot analysis. IOP was measured with a microneedle technique. The eyes were macroscopically examined and histologically analyzed. EGFP expression was detected by confocal microscope. Proteins associated with ODAG were isolated by pull-down assay in conjugation with mass spectrometry.
Macroscopically, ODAG Tg exhibited gradual protrusion of the eyeballs. The mean IOP of ODAG Tg was significantly higher than that of wild-type (WT) littermates. Histologic analysis exhibited optic nerve atrophy and impaired retinal development in the ODAG Tg eye. EGFP was expressed highly in the presumptive outer nuclear layer and weakly in the presumptive inner nuclear layer in the ODAG Tg retina. Rab6-GTPase-activating protein (Rab6-GAP) and its substrate, Rab6, were identified as ODAG-binding proteins.
Deregulated expression of ODAG in the eye induces elevated intraocular pressure and optic nerve atrophy and impairs retinal development, possibly by interfering with the Rab6/Rab6-GAP-mediated signaling pathway. These results provide new insights into the mechanisms regulating ocular development, and ODAG Tg would be a novel animal model for human diseases caused by ocular hypertension.
[Show abstract][Hide abstract] ABSTRACT: To investigate whether the aqueous levels of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) are correlated to the vitreous levels of these substances and to the severity of macular oedema in branch retinal vein occlusion (BRVO).
Aqueous and vitreous samples were obtained during cataract and vitreous surgery from 24 patients (24 eyes) with macular oedema in BRVO. The VEGF and IL-6 levels in aqueous humour, vitreous fluid, and plasma were determined by enzyme-linked immunosorbent assay. The degree of retinal ischaemia was evaluated in terms of the area of capillary nonperfusion using the Scion Image. The severity of macular oedema was evaluated using the OCT.
The aqueous level of VEGF was significantly correlated with the vitreous level of VEGF (P<0.0001). Vitreous levels of VEGF and IL-6 were significantly correlated with the nonperfusion area of BRVO (P<0.0001, P=0.0061, respectively), as were the aqueous levels of VEGF and IL-6 (P<0.0001, P=0.0267, respectively). Furthermore, the vitreous levels of VEGF and IL-6 and the aqueous level of VEGF were significantly correlated with the severity of macular oedema of BRVO (P=0.0001, P=0.0331, P=0.0272, respectively).
Our results suggest that the aqueous level of VEGF may reflect its vitreous level. Measurement of the aqueous level of VEGF may be clinically useful to indicate the severity of macular oedema with BRVO.
[Show abstract][Hide abstract] ABSTRACT: Age-related macular degeneration (AMD) is one of the leading causes of blindness among older adults in developed countries and also in Japan. Previous research suggests that AMD is etiologically a complex disease, caused by multiple genes and environmental factors. Association studies have identified that a complement factor H gene (CFH) variant is a major risk factor for AMD in Caucasians. However, we and two other groups have reported no association between CFH and AMD in the Japanese population. Recent studies have suggested that LOC387715 on chromosome 10q26 may be the second major risk loci for AMD in Caucasians. In this study, we examined the association between LOC387715 and AMD in Japanese, and our results show that polymorphism of the LOC387715 gene is associated with AMD in Japanese as well as in Caucasians. Our data show a disease odds ratio of 6.20 (95% CI: 2.87-13.40) conferred by homozygosity for risk alleles at LOC387715 compared with the non-risk genotype. A polymorphism of LOC387715 gene is associated with AMD in the Japanese population.
[Show abstract][Hide abstract] ABSTRACT: The clinical and genetic relationships between Alzheimer's disease (AD) and glaucoma remain obscure. The aim of this study was to determine the prevalence of open-angle glaucoma (OAG) in patients with AD and whether the apolipoprotein E (APOE) 4 allele is associated with AD, with or without OAG, in Japanese. The groups consisted of 172 patients with the diagnostic criteria of AD and 176 age-matched controls. Ophthalmic examinations were conducted, and genomic analysis was performed by PCR and digestion of products with an enzyme. OAG was found in 41 (23.8%) of the AD patients, which was a significantly (p = 0.0002) higher prevalence than that in the controls (9.9%). Furthermore, there was no significant difference between intraocular pressures (IOPs) in AD patients with OAG and without OAG. The percentage of AD patients who carried an APOE epsilon4 allele (29.5%) was significantly (p = 0.0007) higher than that of the controls (9.1%). However, the percentage of AD patients with OAG who carried an APOE epsilon4 allele (35.7%) was not significantly different than that of AD patients without OAG (27.7%, p = 0.42). In summary, the prevalence of OAG is high in Japanese patients with AD, suggesting that common factors other than APOE may contribute to the two diseases.
Journal of the Neurological Sciences 08/2006; 246(1-2):79-83. · 2.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to determine whether genetic polymorphism of complement factor H (CFH) is associated with age-related macular degeneration (AMD) in the Japanese population.
Genomic DNA was examined in a cohort of 67 Japanese patients with AMD and 107 controls. TT/TC/CC genotypes on exon 9 were screened for sequence alternation by polymerase chain reaction analysis and through sequencing.
The mean ages +/- SD of AMD patients and control subjects were 73 +/- 8.5 years and 72 +/- 8.7 years, respectively. There was no significant difference between CFH genotypes in the AMD group (TT, 76%; TC, 19%; CC, 5%) and the control group (TT, 80%; TC, 17%; CC, 3%). The frequencies of T and C alleles were 86% and 14%, respectively, in the AMD group and 89% and 11%, respectively, in the control group.
CFH gene polymorphism is not associated with AMD in the Japanese population. Moreover, the frequency of the C allele is low among the Japanese population.
[Show abstract][Hide abstract] ABSTRACT: To compare the prevalence of glaucoma in adults with Down's syndrome (DS) to that in non-DS control adults.
Twenty-six patients (14 men and 12 women) with DS and 188 control subjects (105 men and 83 women) were studied. The mean age was 35.1 +/- 6.9 (+/- SD) years in the DS group and 36.9 +/- 5.2 years in the control group. There were no significant differences in age or sex distribution between the two groups. Glaucoma was diagnosed by two glaucoma specialists based on the optic disc findings obtained through dilated pupils.
The prevalence of patients with glaucoma in the DS group was 11.5%, significantly higher (P = 0.014) than that in the control group, 1.1%. There was no significant difference in intraocular pressure between glaucomatous eyes (12.2 +/- 3.2 mmHg) and nonglaucomatous eyes (11.1 +/- 4.1 mmHg) in the DS group (P = 0.465).
The prevalence of glaucoma in adult patients with DS was significantly higher than that in age-matched control subjects.
Japanese Journal of Ophthalmology 01/2006; 50(3):274-6. · 1.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To report the clinical features and surgical and visual outcomes of rhegmatogenous retinal detachment (RRD) in the paediatric population.
A retrospective review of children (aged 0-15 years) who underwent primary surgical repair for RRD at the Hiroshima University Hospital between 1988 and 2001.
In all 53 eyes of 49 patients were identified; paediatric RRD accounted for 3.1% of 1779 eyes with RRD operated on during this period. The causes of RRD included blunt trauma (27%), myopia (25%), idiopathic (20%), familial exudative vitreoretinopathy (13%), and others. Among 55 eyes, 12 (22%) already had proliferative vitreoretinopathy (PVR) of grade C or D preoperatively. The median initial visual acuity (VA) was 0.3. Retinal reattachment was achieved with a single operation in 78%. Final retinal reattachment was achieved in 87%. Retinal reattachment rates with and without PVR were 42% and 100%, respectively (P<0.01). Median final VA was 0.7. Final VA was > or =0.1 in 73% and > or =0.5 in 53%; four eyes had a final VA of no light perception. The presence of preoperative PVR (P=0.03) and the initial VA (P<0.0001) significantly affected final VA.
Paediatric RRD is characterised by a delay in diagnosis, as evidenced by the high rate of PVR at presentation. Retinal reattachment was adversely affected by the presence of PVR. Final VA correlated with the initial VA and was significantly affected by preoperative PVR. Early diagnosis may improve the visual prognosis of paediatric retinal detachment.
[Show abstract][Hide abstract] ABSTRACT: To evaluate whether cognitive impairment improves in elderly patients who have cataract surgery with intraocular lens (IOL) implantation.
Kouki Hospital, Yamaguchi, Japan.
A prospective observational study evaluated patients' scores on the Revised Hasegawa Dementia Scale (HDS-R) and the HDS-R minus 1 item regarding immediate regeneration (ie, function of vision and memory). Twenty patients (6 men, 14 women) with cognitive impairment had cataract surgery in 1 eye between March 1996 and July 2001 at Kouki Hospital, Japan. The mean age of the patients was 81.8 years (range 61 to 90 years). Twenty patients (4 men, 16 women) with cognitive impairment who did not have cataract surgery were selected as a control. The mean age in the control group was 84.3 years (range 70 to 93 years). The HDS-R was administered twice between March 1996 and July 2001.
The mean HDS-R scores in the cataract surgery group improved from 12.5 points +/- 5.3 (SD) preoperatively to 16.6 +/- 6.2 points postoperatively; the improvement was significant (t = -5.02; P<.0001). After cataract surgery, the grade of cognitive impairment improved in 12 patients (60%), was unchanged in 7 (35%), and was worse in 1 (5%).
Cataract surgery improved cognitive impairment in elderly Japanese patients.
Journal of Cataract and Refractive Surgery 03/2004; 30(3):598-602. · 2.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tears of the retinal pigment epithelium are known to occur either spontaneously or after laser photocoagulation in eyes with retinal pigment epithelium detachment. A 65-year-old man with preexisting retinal pigment epithelium detachment developed a retinal pigment epithelium tear after dye laser retinal photocoagulation. The tear gradually expanded to involve the fovea, but his best-corrected visual acuity remained 0.7 in the left eye during 20 months. Optical coherence tomography showed a defect of the retinal pigment epithelium with absence of regeneration. Scanning laser ophthalmoscopy revealed his fixation approached intact retinal pigment epithelium, but was still beneath the fovea. This case may indicate that the retinal pigment epithelium directly beneath the central macula is not essential for maintenance of the overlying foveal function under some conditions.
Ophthalmic Surgery Lasers and Imaging 01/2003; 34(3):217-20. · 1.46 Impact Factor