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PubMedDate not supplied

Ocular findings in Japanese patients with varicella-zoster virus infection.

PURPOSE: To examine ocular findings in Japanese patients with varicella, herpes zoster ophthalmicus, and acute retinal necrosis. METHODS: A retrospective study was conducted. Information on the ocular, cutaneous, systemic, and virologic findings on pediatric and adult patients was obtained from medical records. RESULTS: A total of 77 (45 male and 32 female) patients were enrolled in the study: 4 children had varicella, 68 adults had herpes zoster ophthalmicus, and 5 adults had acute retinal necrosis. Children with varicella had eruptions on the eyelid. Patients with herpes zoster ophthalmicus had eruptions, conjunctivitis, keratitis, iridocyclitis, and other findings. Patients with acute retinal necrosis had intracameral cells and retinal lesions. Some patients with herpes zoster ophthalmicus had malignancy, type 2 diabetes mellitus, or other disease. One pregnant woman developed acute retinal necrosis shortly after varicella infection. A total of 48% of patients with negative Hutchinson sign had ocular lesions, while all patients with positive sign showed ocular lesions. Patients with varicella and herpes zoster ophthalmicus had good visual acuity at the last visit. Some patients with acute retinal necrosis had poor visual acuity at the last visit. CONCLUSIONS: Patients with varicella, herpes zoster ophthalmicus, and acute retinal necrosis had several ocular complications. Some patients with acute retinal necrosis had poor visual outcomes. Ophthalmologists should be aware that acute retinal necrosis may develop shortly after varicella infection.

Adolescent↗
PubMed2006

Retinal pigment epithelium tear after intravitreal bevacizumab for exudative age-related macular degeneration.

PURPOSE: To report on the development of retinal pigment epithelium tears after intravitreal injections of bevacizumab as treatment of exudative age-related macular degeneration (AMD). DESIGN: Interventional case series. METHODS: The study included 63 patients who received an intravitreal injection of 1.5 mg bevacizumab as treatment of a detachment of the retinal pigment epithelium attributable to AMD and who had a follow-up of at least two months. RESULTS: Four patients (6%) developed a tear of the retinal pigment epithelium in the parafoveal region. Compared with the baseline value, visual acuity at the end of follow-up remained stable in three patients and declined in the fourth patient. CONCLUSIONS: Intravitreal injections of bevacizumab may be followed by a tear of the retinal pigment epithelium in eyes with exudative AMD and a retinal pigment epithelium detachment.

Angiogenesis Inhibitors↗
PubMed2006

Temporal regulation of EphA4 in astroglia during murine retinal and optic nerve development.

Eph receptors and their ephrin ligands play important roles in many aspects of visual system development. In this study, we characterized the spatial and temporal expression pattern of EphA4 in astrocyte precursor cell (APC) and astrocyte populations in the murine retina and optic nerve. EphA4 is expressed by immotile optic disc astrocyte precursor cells (ODAPS), but EphA4 is downregulated as these cells migrate into the retina. Surprisingly, mature astrocytes in the adult retina re-express EphA4. Within the optic nerve, EphA4 is expressed in specialized astrocytes that form a meshwork at the optic nerve head (ONH). Our in vitro and in vivo data indicate that EphA4 is dispensable for retinal ganglion cell (RGC) axon growth and projections through the chiasm. While optic stalk structure, APC proliferation and migration, retinal vascularization, and oligodendrocyte migration appear normal in EphA4 mutants, the expression of EphA4 in APCs and in the astrocyte meshwork at the ONH has implications for optic nerve pathologies.

Animals↗
PubMed1998

Math5 encodes a murine basic helix-loop-helix transcription factor expressed during early stages of retinal neurogenesis.

We have identified Math5, a mouse basic helix-loop-helix (bHLH) gene that is closely related to Drosophila atonal and Xenopus Xath5 and is largely restricted to the developing eye. Math5 retinal expression precedes differentiation of the first neurons and persists within progenitor cells until after birth. To position Math5 in a hierarchy of retinal development, we compared Math5 and Hes1 expression in wild-type and Pax6-deficient (Sey) embryos. Math5 expression is downregulated in Sey/+ eyes and abolished in Sey/Sey eye rudiments, whereas the bHLH gene Hes1 is upregulated in a similar dose-dependent manner. These results link Pax6 to the process of retinal neurogenesis and provide the first molecular correlate for the dosage-sensitivity of the Pax6 phenotype. During retinogenesis, Math5 is expressed significantly before NeuroD, Ngn2 or Mash1. To test whether these bHLH genes influence the fates of distinct classes of retinal neurons, we ectopically expressed Math5 and Mash1 in Xenopus retinal progenitors. Unexpectedly, lipofection of either mouse gene into the frog retina caused an increase in differentiated bipolar cells. Directed expression of Math5, but not Xath5, in Xenopus blastomeres produced an expanded retinal phenotype. We propose that Math5 acts as a proneural gene, but has properties different from its most closely related vertebrate family member, Xath5.

Amino Acid Sequence↗
PubMed2000

Visual acuity outcomes with and without surgery in patients with persistent fetal vasculature.

PURPOSE: To investigate visual acuity outcomes in patients with persistent fetal vasculature (PFV) left untreated or treated with vitreoretinal surgical techniques and to investigate clinical features associated with prognosis. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: All patients with PFV examined at the Bascom Palmer Eye Institute from January 1, 1983 through December 31, 1998. INTERVENTION: All patients in the study had unilateral PFV. Of 42 PFV patients identified, 30 patients underwent vitreoretinal surgery. Indications for surgery included media opacity (e.g., cataract), vitreoretinal traction, and retinal detachment. MAIN OUTCOME MEASURES: Final best postoperative visual acuity, prognostic ocular clinical features, and surgical complications. RESULTS: In the surgical group of patients, median age at diagnosis was 8 weeks, and median length of follow-up was 32 months, with all patients having at least 1 year of follow-up. Two patients had clinical and echographic findings consistent with anterior PFV, 2 patients had strictly posterior PFV, and the remaining 26 patients had components of both anterior and posterior PFV. Fourteen eyes (47%) achieved a final visual acuity of 20/400 or better at last follow-up. Risk factors for a poor visual acuity outcome (<20/400) included microphthalmia (28% of patients with microphthalmia versus 67% of patients with normal axial length achieved a final vision of 20/400 or better; P = 0.061) and preoperative retinal detachment or retinal or optic nerve abnormalities, or both, such as hypoplasia, folds, or indistinct macula with hypopigmentation (25% of patients with any of these anomalies versus 61 % of patients without these findings achieved a final vision of 20/400 or better; P = 0.072). After surgery, retinal detachment developed in three eyes, chronic hypotony in two other eyes, and neovascular glaucoma in one eye. In the nonsurgical group there were 6 male and 6 female patients. Two patients with posterior PFV had minimal disease and were not considered surgical candidates, whereas 10 patients with combined anterior and posterior PFV had advanced pathologic features, and it was believed that surgery would not offer significant visual improvement; median age at diagnosis was 9.5 months, and median length of follow-up was 36 months, with all patients having at least 1 year of follow-up. At last follow-up, 3 eyes (25%) had a final visual acuity of 20/400 or better. During follow-up, retinal detachment developed in 2 eyes and chronic hypotony in an additional 2 eyes. CONCLUSIONS: The current study indicates that approximately 50% of patients undergoing surgery for PFV will achieve useful vision. Visual acuity outcomes in patients with PFV are correlated with the nature and extent of ocular risk factors. Some patients may not be candidates for surgery because of either minimal changes or advanced disease that limit the potential of visual improvement.

Cataract Extraction↗
PubMed1992

Characterization of acetylcholinesterase and butyrylcholinesterase activities in retinal chick pigment epithelium during development.

The presence of acetylcholinesterase and butyrylcholinesterase was studied in chick retinal pigment epithelium. Acetylcholinesterase activity was 13 times higher than that of butyrylcholinesterase. The former showed a Km of 290 microM and a vmax of 45.4 nmol mg-1 protein min-1, while the latter showed two apparent Km values (132 microM and 666 microM). Studies on subcellular distribution revealed that both enzymes are associated with membranes. During the embryonic development butyrylcholinesterase activity decreased, while acetylcholinesterase activity increased. The possibility that these changes are related to the proliferation and differentiation processes is discussed.

Acetylcholinesterase↗
PubMedDate not supplied

Development of the rabbit retina, III: Differential retinal growth, and density of projection neurons and interneurons.

To provide a quantitative description of postnatal retinal expansion in rabbits, a new procedure was developed to map the retinae, which cover the inner surface of hemispheres or parts of rotation ellipsoids, in situ, onto a single plane. This method, as well as the known distribution of Müller cells per unit retinal surface area, were used to estimate the redistribution of specific subpopulations of Müller cells within different topographic regions of the retinae. Müller cells are known to exist as a stable population of cells 1 week after birth and can therefore be used as "markers" for determining tissue expansion. Our results show that differential retinal expansion occurs during development. Peripheral retinal regions expand at least twice as much as the central ones. Furthermore, there is a greater vertical than horizontal expansion. This differential retinal expansion leads to a corresponding redistribution of 5-hydroxytryptamine (5-HT) accumulating amacrine cells. Differential retinal expansion, however, does not account for all of the changes in the centro-peripheral density gradient of cells in the ganglion cell layer (GCL)--mostly retinal ganglion cells--during postnatal development. The changes in the ganglion cell layer were evaluated in Nissl-stained wholemount retinal preparations. Additionally, the difference between expansion-related redistribution of cells in the GCL and Müller cells was confirmed in wholemount preparations where Müller cells (identified as vimentin positive) and cells in the GCL (identified by fluorescent supravital dyes) were simultaneously labeled. It is assumed that many of the ganglion cells within the retinal center are not translocated during retinal expansion, possibly because their axons are fixed. In contrast, 5-HT accumulating amacrine cells--which are interneurons without a retinofugal axon--display a passive redistribution together with the surrounding retinal tissue.

Animals↗
PubMed1985

Increase in actin contents and elongation of apical projections in retinal pigmented epithelial cells during development of the chicken eye.

The structural and biochemical changes of cytoskeletal components of retinal pigmented epithelial cells were studied during the development of chicken eyes. When the cytoskeletal components of the pigmented epithelial cells from various stages of development were examined by SDS PAGE, actin contents in the cells markedly increased between the 15-d-old and hatching stages. Immunofluorescence microscopy showed that chicken pigmented epithelial cells have two types of actin bundles. One is the circumferential bundle associated with the zonula adherens region as previously reported (Owaribe, K., and H. Masuda, 1982, J. Cell Biol., 95:310-315). The other is the paracrystalline bundle forming the core of the apical projections. The increase in actin contents after the 15-d-old stage is accompanied by the formation and elongation of core filaments of apical projections in the cells. During this period the apical projections extend into extracellular space among outer and inner segments of photoreceptor cells. Accompanying this change is an elongation of the paracrystalline bundles of actin filaments in the core of the projection. By electron microscopy, the bundles decorated with muscle heavy meromyosin showed unidirectional polarity, and had transverse striations with approximately 12-nm intervals, as determined by optical diffraction of electron micrographs. Since the shape of these bundles was not altered in the presence or absence of Ca2+, they seemed not to have villin-like proteins. Unlike the circumferential bundles, the paracrystalline bundles did not contract when exposed to Mg-ATP. These observations indicate that the paracrystalline bundles are structurally and functionally different from the circumferential actin bundles.

Actins↗
PubMed1991

Retinal artery obstruction and atheromas associated with non-Hodgkin's large cell lymphoma (reticulum cell sarcoma).

A 71-year-old woman developed branch retinal artery obstruction as the presenting manifestation of a large cell non-Hodgkin's lymphoma. Multifocal chorioretinal scars were present in the same eye. She experienced progressive visual loss accompanied by development of multiple yellow retinal arterial wall plaques, extension of retinal opacification into other quadrants, and increasing vitreous cellular infiltration. Clinical diagnoses included branch retinal arterial obstruction caused by toxoplasmosis retinitis, multifocal choroiditis and panuveitis simulating the presumed ocular histoplasmosis syndrome, vitiliginous chorioretinitis, and the acute retinal necrosis syndrome. Four months after onset, the right eye was blind and was enucleated. Histopathologic examination revealed extensive lymphomatous infiltration and necrosis of the retina and optic nerve. The retinal arteries were partly obstructed by lymphomatous infiltration and atheromas. Subsequently, the left eye and central nervous system were involved by lymphoma.

Aged↗
PubMed2000

Angiopoietin 2 expression in the retina: upregulation during physiologic and pathologic neovascularization.

Vascular development in the embryo requires coordinated signaling through several endothelial cell-specific receptors; however, it is not known whether this is also required later during retinal vascular development or as part of retinal neovascularization in adults. The Tie2 receptor has been implicated in stabilization and maturation of vessels through action of an agonist ligand, angiopoietin 1 (Ang1) and an antagonistic ligand, Ang2. In this study, we have demonstrated that ang2 mRNA levels are increased in the retina during development of the deep retinal capillaries by angiogenesis and during pathologic angiogenesis in a model of ischemic retinopathy. Mice with hemizygous disruption of the ang2 gene by insertion of a promoterless beta-galactosidase (beta gal) gene behind the ang2 promoter, show constitutive beta gal staining primarily in cells along the outer border of the inner nuclear layer identified as horizontal cells by colocalization of calbindin. During development of the deep capillary bed or retinal neovascularization, other cells in the inner nuclear layer and ganglion cell layer, in regions of neovascularization, stain for beta gal. Thus, there is temporal and spatial correlation of Ang2 expression with developmental and pathologic angiogenesis in the retina, suggesting that it may play a role.

Angiopoietin-1↗
PubMed2005

Incidence of cytomegalovirus (CMV) retinitis in second eyes of patients with the acquired immune deficiency syndrome and unilateral CMV retinitis.

PURPOSE: To evaluate the risk and risk factors for developing cytomegalovirus (CMV) retinitis in previously uninvolved second eyes among patients with unilateral CMV retinitis. DESIGN: Cohort study. METHODS SETTINGS: Single-center academic AIDS ophthalmology practice. PATIENT POPULATION: Three hundred seventy-six consecutive patients with AIDS and unilateral CMV retinitis were followed from the time of CMV retinitis diagnosis for the development of second-eye retinitis. EXPERIMENTAL PROCEDURES: Demographic and clinical characteristics were noted at baseline. Use of highly active antiretroviral therapy (HAART) and immune recovery in response to HAART were noted prospectively. MAIN OUTCOME MEASURE: Development of CMV retinitis in a previously uninvolved eye. RESULTS: Ninety-one percent of subjects received systemic anti-CMV treatment. Second-eye retinitis occurred in 26.1%/person-year (19.6% within the first 6 months), less than half the rate previously reported in untreated groups. Initial CD4+ T cell count >12 cells/microl, use of HAART, and initial posterior pole involvement were associated with 64%, 46%, and 41% reductions in incidence vis-à-vis comparison groups. Benefit from HAART was limited to that subset who developed immune recovery of a degree expected to restore innate control of CMV (a rise in the CD4+ T cell count by >50 cells/microl to a level >100 cells/microl). CONCLUSIONS: The risk of second-eye retinitis is substantial in patients with unilateral CMV retinitis but appears to be reduced by anti-CMV therapy and by HAART-induced immune recovery. Patients are at highest risk when CD4+ T cell counts are very low and in the months immediately after CMV retinitis diagnosis.

AIDS-Related Opportunistic Infections↗
PubMed1987

Growth and development of the mouse retinal pigment epithelium. II. Cell patterning in experimental chimaeras and mosaics.

The retinal pigment epithelium (PE), with pigmentation as a cell-autonomous marker, was analyzed in three types of mice: congenic pigmented----albino chimaeras, X-inactivation mosaics (Cattanach's translocation), and mosaics homozygous for the pink-eyed unstable mutation, which contain rare fully pigmented cells. In 10 chimaeric and 34 X-inactivation eyes, the proportionate mix in the right and left eyes of an individual animal was similar, the mix was approximately constant in all parts of a given eye, average patch size was larger toward the periphery of the PE, and peripheral patches tended to be elongated in the radial dimension. In all 44 whole mounts from pink-eyed unstable mutants, patches of 1-12 pigmented cells, each representing a single clone, were scattered throughout the PE; they tended to be larger with increasing distance from the optic nerve head. The collective data are consistent with significant cell mixing prior to specification of the two eye fields, during early organ-forming stages, and during later development of the PE. The tendency of peripheral patches to orient radially reflects the edge-biased pattern of cell proliferation in the PE. Cell mixing appears to be more prominent posteriorly in the PE sheet; growth proceeds anteriorly for more generations.

Animals↗
PubMed1975

Retinal ischemia in diabetic retinopathy.

Eight patients with proliferative diabetic retinopathy developed extensive retinal arteriolar and capillary obstruction. Ophthalmoscopy showed many white, thread-like retinal arterioles associated with capillary and venous dilatation. Widespread retinal arteriolar and capillary nonperfusion was demonstrated by fluorescein angiography. Ischemic maculopathy resulted in severe loss of visual acuity in some eyes. The severe degree of retinal ischemia was accompanied by optic disc pallor and neovascularization and a high incidence of rubeosis iridis with neovascular glaucoma. Patients with this variety of diabetic retinopathy have a poor prognosis of retaining useful vision.

Adolescent↗
PubMed1984

Deferoxamine (Desferal)-induced toxic retinal pigmentary degeneration and presumed optic neuropathy.

Eight patients (16 eyes) developed ocular toxicity while undergoing intravenous deferoxamine mesylate (Desferal) chelation therapy for transfusional hemosiderosis. Presenting symptoms included decreased visual acuity, color vision abnormalities, and night blindness. Six patients presented as presumed retrobulbar optic neuropathy demonstrating central scotomas and color vision abnormalities. The remaining two patients presented with pigmentary changes confined either to the macula or equator. Following cessation of therapy, vision improved in all but four eyes, which did not attain their pretreatment visual acuity. Optic neuropathy resolved in all cases. However, follow-up revealed development of retinal pigmentary degeneration in seven patients, involving the macula in six and the equatorial retina in one. Fluorescein angiography and electrophysiological tests suggested toxicity at the level of retinal pigment epithelium and photoreceptors.

Aged↗
PubMed2003

Hypoxic oxygen fluctuations produce less severe retinopathy than hyperoxic fluctuations in a rat model of retinopathy of prematurity.

The aim of this study was to investigate whether the mean around which arterial oxygen fluctuations take place was important in a unique animal model of oxygen-induced retinopathy. Retinopathy of prematurity (ROP) is associated with fluctuating arterial oxygen. A recent retrospective study suggested that management of high-risk preterm infants at lower oxygen saturations was associated with less severe ROP. Rat pups were raised in a variable oxygen environment around a high (24%), normal (21%) or low (17%) mean inspired oxygen for 14 d. Rat pups raised in the high (24%) mean variable oxygen environment had more retarded retinal vascular development than did rats raised in an environment that fluctuated around 21% mean oxygen. In contrast, rats raised in a lower mean (17%) but still variable oxygen environment had no discernible retinal differences from controls raised in constant room air. Rats raised in a relatively hypoxic but variable oxygen environment develop less severe retinal vascular abnormalities than those raised in variable oxygen around higher oxygen means.

Animals↗
PubMed1997

Sonic hedgehog promotes rod photoreceptor differentiation in mammalian retinal cells in vitro.

The hedgehog gene family encodes secreted proteins important in many developmental patterning events in both vertebrates and invertebrates. In the Drosophila eye disk, hedgehog controls the progression of photoreceptor differentiation in the morphogenetic furrow. To investigate whether hedgehog proteins are also involved in the development of the vertebrate retina at stages of photoreceptor differentiation, we analyzed expression of the three known vertebrate hedgehog genes. We found that Sonic hedgehog and Desert hedgehog are expressed in the developing retina, albeit at very low levels, whereas Indian hedgehog (Ihh) is expressed in the developing and mature retinal pigmented epithelium, beginning at embryonic day 13. To determine whether hedgehog proteins have activities on developing retinal cells, we used an in vitro system in which much of retinal histogenesis is recapitulated. N-terminal recombinant Sonic Hedgehog protein (SHH-N) was added to rat retinal cultures for 3-12 d, and the numbers of retinal cells of various phenotypes were analyzed by immunohistochemistry. We found that SHH-N caused a transient increase in the number of retinal progenitor cells, and a 2- to 10-fold increase in the number of photoreceptors differentiating in the cultures when analyzed with three different photoreceptor-specific antigens. In contrast, the numbers of retinal ganglion cells and amacrine cells were similar to those in control cultures. These results show that Hedgehog proteins can regulate mitogenesis and photoreceptor differentiation in the vertebrate retina, and Ihh is a candidate factor from the pigmented epithelium to promote retinal progenitor proliferation and photoreceptor differentiation.

Animals↗
PubMed1993

Central retinal area is not the site where ganglion cells are generated first.

The development of retinal ganglion cells (RGC) was studied in the chick from stage 18 to adulthood. Our main objectives were to identify the retinal site where the first RGCs differentiate, to locate this site relative to the optically defined central retinal area, and to map the spatial arrangement of the RGC field at different stages in development. The eyes of the experimental animals were fixed and serially sectioned. The borders of RGC fields were determined from the presence of either ganglion cell perikarya or ganglion cell axons. In seven cases between stages 21 and 26, the borders of the RGC fields were confirmed electron microscopically. The serial sections together with the RGC fields were then reconstructed in three dimensions. The reconstructed retinae were projected onto a plane by using the radially equidistant polar azimuthal projection. First, RGCs appear dorsal to the apex of the optic fissure. Ganglion cell development then initially spreads out symmetrically with respect to the optic fissure. However, from stage 29 on, the nasal half of the retina expands much more than the temporal half. This asymmetrical growth entails that the optic fissure is eventually located in the temporal half of the retina in the mature animal. The RGC fields of the embryonic stages were superimposed on the retina of a visually active animal according to their real size and position. It turned out that the central retinal area was at least 2 mm away from the site where the first RGCs were generated. It is not before stage 28 that the prospective central retinal area is included into the expanding ganglion cell field. The fact that RGCs at the central retinal area are generated 2.5 days later than first RGCs near the apex of the optic fissure has important implications for the formation of the retinotectal projection.

Animals↗
PubMed1992

Immunity and immune privilege elicited by autoantigens expressed on syngeneic neonatal neural retina grafts.

Achieving the long-term goal of successful engraftment of retinal tissues into eyes blinded by endogenous retinal failure will depend, at least in part, on controlling the immune response to antigens expressed on retinal grafts. Since histoincompatible tissues will have to be used for such transplants, methods to control immune rejection directed at transplantation alloantigens must be devised. In addition, it has recently been observed in mice that developing neural retinal tissues express retina-specific antigens that have the potential to contribute to graft failure. To examine the potential risk of this contribution, syngeneic neonatal neural retinas were implanted into the anterior chamber, vitreous cavity, and subconjunctival space of adult BALB/c mice. During two weeks post-implantation, the fate of these grafts was observed clinically and histologically, and the retina-specific immune responses of the recipients were evaluated. Whereas grafts placed intraocularly thrived, carried out their inherent developmental potential, and were healthy and intact at the end of the observation interval. Grafts placed extraocularly expressed their differentiation program poorly. These grafts underwent rapid decline and attrition, although the process was not accompanied by significant inflammation. Recipients of subconjunctival, but not AC or VC, implants developed retina-specific delayed hypersensitivity. Alternatively, mice bearing AC and VC implants of neonatal neural retina developed retina-specific anterior chamber associated immune deviation. It is concluded that retinal autoantigens are expressed on developing neural retinal tissues and these antigens are highly immunogenic when retinal grafts are placed at conventional body sites. When similar grafts are placed in immune privileged compartments of the normal eye, they enjoy significant survival. Circumstantial evidence indicates that intraocular retinal grafts are protected and maintained in part by the emergence of systemic retinal auto-antigen-specific immune suppression.

Animals↗