Elevated Intraocular Pressure, Optic Nerve Atrophy, and Impaired Retinal Development in ODAG Transgenic Mice

PURPOSE. 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. METHODS. 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 pulldown assay in conjugation with mass spectrometry. RESULTS. 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. CONCLUSIONS. 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. (Invest Ophthalmol Vis Sci. 2009;50:242-248) DOI:10.1167/iovs.08-2206 O cular development is a complex process, involving several genes with expression that is strictly controlled in a spatial and temporal manner. Although several genes, including Pax6, Rx, and Crx, are essential for normal ocular formation, 1-3 the molecular mechanism(s) governing eye development has not been fully elucidated. To identify genes that are preferentially expressed in the developing eye, we performed a differential display using mRNAs extracted from postnatal day (P)2 and P10 mouse eyes. 4 At P2, ODAG was highly expressed in all the retinal layers (presumptive outer nuclear layer [ONL], presumptive inner nuclear layer [INL], and ganglion cell layer [GCL]), but at P7, its expression decreases, especially in the GCL, and at P14, no apparent expression is detected. To investigate, we generated transgenic mice overexpressing ODAG (ODAG Tg). The mouse Crx promoter, which directs transgene expression in photoreceptors, From th

Eyelid Lengthening Combined with Penetrating Keratoplasty for Exposure Keratopathy in Graves' Ophthalmopathy-A case report

Upper eyelid retraction is a well-known component of Graves' disease. With greater degrees of retraction, corneal exposure is usually increased. We report here on a patient with corneal perforation following exposure keratopathy due to upper eyelid retraction. The patient was treated with penetrating keratoplasty and an upper eyelid lengthening procedure using Goretex^[○!R] dura substitute as an interpositional graft material. The exposure keratopathy resolved postoperatively and this condition has been maintained for 45 months since the operation, with a good cosmetic outcome and symmetry of the palpebral fissures

Results of Filtering Surgery in Young Patients with Aniridia

To evaluate whether filtering surgery is effective in controlling the intraocular pressure of young aniridic patients with glaucoma, we retrospectively reviewed the charts of aniridic patients with glaucoma under the age of 40 years. We defined a good intraocular pressure control period as the time from surgery until IOP exceeded 20 mm Hg, with or without glaucoma medication. Twenty filtering surgeries (17 trabeculectomies and 3 trabeculectomies with mitomycin C) were performed on 10 eyes in 6 patients for more than 20 years. The mean good intraocular pressure control period after the filtering surgery was 14.6 months (range, 2 to 54 months). Aside from mild choroidal detachment, no other serious complications were encountered. We believe that filtering surgery is efficacious for control of intraocular pressure of young aniridic patients with glaucoma

Contact Probe Based Stiffness Sensing of Human Eye

Abstract.The internal eye pressure is an important index for judging whether an eye suffers from glaucoma or not. The conventional eye pressure measurement is valid only under the condition that all subjects have the same structural eye stiffness. This paper challenges stiffness sensing of the human eye by pressing it with a contact probe. The displacement of the eye is captured by a camera with high resolution (see Fig.1). Experimental results show that the stiffness is roughly constant for each subject, while it differs by up to a factor of five between subjects. The method can detect subjects whose eye stiffness is smaller than average for further careful medical examination

High frequency of open-angle glaucoma in Japanese patients with Alzheimer's disease

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 ε4 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 ε4 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

A Five-year Review of Patients Admitted with the Diagnosis of Bacterial Endophthalmitis

We conducted a retrospective, hospital-based study of patients who were diagnosed with bacterial endophthalmitis on admission to the Department of Ophthalmology, Hiroshima University Hospital, between January 1999 and December 2003. Thirty eyes of 30 patients were identified. Of these patients, 19 eyes had postoperative endophthalmitis, 8 eyes had penetrating trauma and 3 eyes were infected from an endogenous source. All of the patients underwent immediate three-port pars plana vitrectomy. Vitreous specimens of diabetic patients demonstrated a significantly higher incidence of positive bacterial culture. Diabetic vitreous appeared to be a good medium for culture. Visual acuity of hand motion or less at the latest follow-up visit was associated with the presence of diabetes. Prompt treatment with vitrectomy and intravitreal antibiotics is crucial for patients with bacterial endophthalmitis, especially if they are diabetic