Atsuhiro Tanikawa

Regulation of rod phototransduction machinery by ciliary neurotrophic factor

Ciliary neurotrophic factor (CNTF) promotes photoreceptor survival but also suppresses electroretinogram (ERG) responses. This has caused concerns about whether CNTF is detrimental to the function of photoreceptors because it is considered to be a potential treatment for retinal degenerative disorders. Here we report that the suppression of ERG responses is attributable to negative regulation of the phototransduction machinery in rod photoreceptors. Intravitreal injection of recombinant human CNTF protein in rat results in a series of biochemical and morphological changes in rod photoreceptors. CNTF induces a decrease in rhodopsin expression and an increase in arrestin level. Morphologically, CNTF treatment causes a shortening of rod outer segments (ROS). All of these changes are fully reversible. The lower rhodopsin level and shortened ROS reduce the photon catch of rods. Less rhodopsin and more arrestin dramatically increase the arrestin-to-rhodopsin ratio so that more arrestin molecules are available to quench the photoexcited rhodopsin. The overall effect of CNTF is to negatively regulate the phototransduction machinery, which reduces the photoresponsiveness of rods, resulting in lower ERG amplitude at a given intensity of light stimulus. The CNTF-induced changes in rods are similar to those in light-induced photoreceptor plasticity. Whether CNTF-induced changes in rods are through the same mechanism that mediates light-induced photoreceptor plasticity remains to be answered.

Basic study of retinal stem/progenitor cell separation from mouse iris tissue

We described the possibility of retinal regeneration using a novel and efficient technique for culturing and separating retinal stem/progenitor cells from iris tissue. Immunohistochemical staining of adult agouti mouse iris tissue revealed the presence of nestin/low-affinity neurotrophin receptor p75 (p75NTR)-positive cells on the endothelium camerae anterioris side. Cultured mouse iris-derived cells contained little or no melanin and were found to be positive for nestin. Most nestin-positive cells were analyzed for the coexpression of p75NTR as a cell membrane protein. When the p75NTR was used as a marker to sort the cells, we obtained a dense population of nestin-positive cells. Furthermore, the nestin/p75NTR-positive cells were able to differentiate into neural retina cells. Thus, this culture and separation technique is useful for obtaining retinal stem/progenitor cells from adult mouse iris tissue and for the efficient production of neural retina cells.

Cultured human corneal epithelial stem/progenitor cells derived from the corneal limbus.

Stem/progenitor cells of the human corneal epithelium are present in the human corneal limbus, and several corneal epithelial stem/progenitor cell markers have been reported. Recently, the neurotrophin family receptors were reported to be useful markers of corneal epithelial stem/progenitor cells. Therefore, we examined an enzymatic separation method for obtaining corneal epithelial stem/progenitor cells and measuring the change in the expression of low-affinity neurotrophin receptor p75 (p75NTR), a receptor belonging to the neurotrophin family. As a result, it was found that our separation method preserved cell viability. Furthermore, p75NTR was mainly observed in epithelial basal cells as were the corneal epithelial stem/progenitor markers p63 and integrin β1. p75NTR was also observed in the cultured cells, but its frequency decreased with passage. In conclusion, we propose that our culture method will enable the culture of corneal stem cells and that it is a useful tool for elucidating the molecular basis of the niche that is necessary for the maintenance of epithelial stem cells in the corneal limbus. Furthermore, we conclude that p75NTR is a useful cell marker for evaluating the characteristics of stem/progenitor cells in culture.

Congenital toxoplasmosis mimicking microcephaly-lymphedema-chorioretinal dysplasia

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Electroretinograms in three cases of Creutzfeldt-Jakob disease with visual disturbances

PurposeTo report three cases of idiopathic Creutzfeldt-Jakob disease (CJD) with visual symptoms.CasesPatient 1 initially visited our ophthalmology department complaining of blurred vision. Electro-retinography (ERG) showed a selective reduction of the b wave before she was diagnosed with CJD. Patient 2 had normal ERG results even with severely advanced CJD. However, a reduction of the b wave on ERG was observed 1 month before the patient died. Patient 3 had visual disturbances at the initial visit, but the ERG result was normal even after the CJD had advanced. Atrophy of the visual cortex was later observed.ObservationsCJD can alter the vision in various ways. The selective reduction of the b wave on ERG indicates the retinal involvement. However, visual disturbances may occur without the retinal implications.ConclusionOphthalmologists should be aware that the visual impairment can be the first symptom of CJD.

Comparison of visual acuity, metamorphopsia, and aniseikonia in patients with an idiopathic epiretinal membrane

PurposeThe clinical course of reduced visual acuity, metamorphopsia, and aniseikonia are dissimilar in patients with an epiretinal membrane (ERM). We measured and compared the best-corrected visual acuity (BCVA), metamorphopsia, and aniseikonia of patients with ERM.MethodsWe measured metamorphopsia and aniseikonia horizontally as well as vertically with the M-CHART (MH and MV) and New Aniseikonia Test (NATH and NATV) in 61 patients with unilateral idiopathic ERM. We compared the BCVA with the other values. Comparisons between the MH and the NATV and between the MV and the NATH were performed, because the MH assesses vertical metamorphopsia, and the MV, horizontal metamorphopsia.ResultsBCVA was not significantly correlated with the other values (MH vs BCVA: P = .69; MV vs BCVA: P = .114; NATH vs BCVA: P = .656; NATV vs BCVA: P = .935). The MH and NATV magnitudes were significantly correlated, but the correlation coefficient was small (P = .007, r = 0.343); no significant correlation was found between the MV and NATH magnitudes (P = .065). We found patients with aniseikonia, but no metamorphopsia (n = 6), and more patients with metamorphopsia, but no aniseikonia (n = 11). Only 23 patients had coincident directions of metamorphopsia and aniseikonia.ConclusionsThe magnitudes of metamorphopsia and aniseikonia were not closely correlated and their directions did not coincide in most patients. Neither the M-CHARTS nor the NAT measurements correlated with the BCVA. Quantitative testing of metamorphopsia and aniseikonia in addition to that for BCVA is necessary to assess visual function in patients with ERM.

A Case of Bilateral Optic Nerve Head Drusen-Induced Inferior Altitudinal Hemianopsia

ABSTRACT The current case involved a 59-year-old woman who was referred to our hospital with bilateral optic nerve abnormality and gradually progressive bilateral inferior visual field defects. An ophthalmological examination revealed superficial optic nerve head drusen (ONHD) and bilateral inferior altitudinal hemianopsia, but no intracranial lesions. The results of an angiogram revealed no evidence of retinal vascular occlusion or anterior ischaemic optic neuropathy (AION). Prior reports suggested that drusen-induced hemianopsia was slowly progressive but that ONHD-induced AION caused acute altitudinal hemianopsia, which led us to the diagnosis of bilateral drusen-induced altitudinal hemianopsia.

Intravitreal Triamcinolone–Illuminated Cataract Surgery for Patients With Dense Vitreous Hemorrhage

Almost all cataract surgical procedures rely on phacoemulsification, which requires favorable lens visibility. Visibility can be negatively affected by various ocular pathologies including dense vitreous hemorrhage. When the microscope light source reflects off the ocular fundus, the lens is transilluminated. In the presence of dense vitreous hemorrhage, light cannot adequately reach the fundus, and no red reflex is created. In these patients, vitrectomy and cataract surgery may be performed simultaneously (phacovitrectomy) but cataract surgery complications, such as nucleus drop or corneal damage, may lead to problems during vitrectomy. Several surgical techniques have been used to alleviate the problem of poor lens visibility.1,2 Jang et al1 fixed a chandelier illuminator on the sclera, turned off the microscope light source, and visualized the lens by illuminating the vitreous cavity. Furino et al2 improved anterior lens capsule visibility by staining it with triamcinolone acetonide. Although both techniques were effective, both had limitations. Vitreous chamber illumination reduces the visibility of the cornea and iris because of the need to turn off the microscope light. Staining the anterior lens capsule with triamcinolone acetonide allows for better anterior chamber visualization but the lenticular nucleus and cortex remain difficult to see. Here, we present a novel surgical technique, to our knowledge, in which triamcinolone acetonide is injected into the vitreous cavity before vitrectomy. In the absence of a red reflex, cataract surgery is performed using the white reflex created by the light from the microscope reflecting off triamcinolone acetonide crystals in the vitreous. This allows the cornea, anterior chamber, iris, lens nucleus, lens cortex, and posterior chamber to be easily viewed, potentially improving the safety of cataract surgery in these patients. This surgical technique was reviewed and approved by the Fujita Health University institutional review board. This study adhered to the Declaration of Helsinki tenets, and all patients provided written informed consent. A total of 23 patients with poor lens visibility due to dense vitreous hemorrhage were included. All patients required vitrectomy and cataract surgery independent of the study. No exclusion criteria were applied.