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PubMed2006

Successful anticoagulation for bilateral central retinal vein occlusions accompanied by cerebral venous thrombosis.

BACKGROUND: Concurrent development of retinal venous drainage and cerebral venous thrombosis has not been reported. Case Description We describe a 23-year-old man with bilateral central retinal vein occlusions and cerebral venous thrombosis. Initially observed bilateral hemorrhagic retinopathy and thrombus in the right transverse sinus of the patient began to resolve after 2 weeks of low-molecular-weight heparin. Hemorrhagic retinopathy progressively improved to previous visual acuity and the right lateral sinus remained patent by maintenance of anticoagulation with warfarin. CONCLUSION: The present case shows effectiveness of low-molecular-weight heparin for the initial management of hemorrhagic retinopathy of central retinal vein occlusion combined with cerebral venous thrombosis.

Adult↗

PubMed1987

Cone-mediated retinal function in cats during development.

Cone electroretinograms (ERGs) were recorded in kittens from 25 to 150 days of age and in adult cats. B-wave amplitudes in kittens between 25 and 94 days of age were either within the adult range or greater than adult responses. After about 100 days, all kittens had adult-like amplitudes. Cone b-wave implicit time was markedly prolonged at the earliest ages tested and only after 80 days was the timing like that in adult cats. Amplitude and timing of 40-Hz flicker ERGs confirmed the single flash cone ERG data. Critical flicker fusion frequency was mature by 74 days of age. These findings, taken together with previous results, indicate that there are differences in the time course of development of cone- and rod-mediated retinal function in the cat.

Aging↗

PubMed2004

Retinal vein occlusions in patients taking warfarin.

OBJECTIVE: To describe development of retinal vein occlusion (RVO) in patients anticoagulated with warfarin. DESIGN: Retrospective, observational case series. PARTICIPANTS: Thirteen patients drawn from a private retina practice. METHODS: Review of clinical records, laboratory results, color fundus photographs, and fluorescein angiograms. MAIN OUTCOME MEASURES: Primary measures were international normalized ratio (INR), visual acuity, and concurrent systemic disease. RESULTS: The female-to-male ratio was 7 to 6. Age range was 44 to 86 years, with a median age of 73 years. Two patients had systemic lupus erythematosus, 7 had hypertension, and 2 had primary open-angle glaucoma. Two had laboratory abnormalities: 1 with a combination of lupus anticoagulant and anticardiolipin antibodies and 1 with a combination of hyperhomocystinemia and low antithrombin III. Three patients were taking acetylsalicylic acid in addition to warfarin at the time of the RVO. The INRs at the time of RVO were 0.9 to 3.8, with 9 of 13 <==2.0. CONCLUSIONS: Anticoagulation with warfarin does not preclude RVO in predisposed patients, nor does combination therapy with warfarin and acetylsalicylic acid. Attention to keeping the INR >2.0 may be helpful.

Adult↗

PubMed1995

Vascular endothelial growth factor/vascular permeability factor expression in a mouse model of retinal neovascularization.

Neovascular diseases of the retina are a major cause of blindness worldwide. Hypoxia is thought to be a common precursor to neovascularization in many retinal diseases, but the factors involved in the hypoxic neovascular response have not been fully identified. To investigate the role of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) in retinal neovascularization, the expression of VEGF/VPF mRNA and protein were studied in a mouse model of proliferative retinopathy. RNA (Northern) blot analysis revealed that retinal VEGF/VPF mRNA expression increased 3-fold between 6 and 12 hr of relative retinal hypoxia and remained elevated during the development of neovascularization. In situ hybridization localized VEGF/VPF mRNA to cells bodies in the inner nuclear layer of the retina. Immunohistochemical confocal microscopy demonstrated that VEGF/VPF protein levels increase with a time course similar to that of the mRNA. The cells in the inner nuclear layer of the retina that produce VEGF/VPF were identified morphologically as Müller cells. These data suggest that VEGF/VPF expression in the retina plays a central role in the development of retinal ischemia-induced ocular neovascularization.

Animals↗

PubMed1985

[Chorioretinopathy caused by migration of caterpillar hairs. Apropos of 2 cases].

Caterpillars cause many ocular lesions by a pathogen agent coming from their coating: the hairs. These can enter into the eye ball and migrate in the ocular tissues; a secondary inflammatory reaction to the foreign body will appear. This reaction is due to the hairs themselves as foreign body, but also partly to their contents: a liquid toxin which contains proteins, lipids and other components. The morphological configuration of the hair favours its migration in the tissues. Among the different lesions observed, chorio retinopathies are not very frequent, but their clinical aspect is quite characteristic and they are easier to recognize when they are associated with intra crystalline caterpillar hairs. Two cases of chorio retinopathies had been recorded. Both had hairs inside the lens and important hyalitis. One had the very characteristic "track-shaped" scars in the eye-fundus. The other had a focal chorio retinitis above the inferior temporal artery and developed a retinal tear. Local and general corticotherapy was applied, but the effect was not adequate. Vitrectomy was performed in the two patients with a good functional result. This seems to prove that vitrectomy may be useful for the important hyalitis secondary to the intra ocular migration of caterpillar hairs.

Adolescent↗

PubMed1998

Retinal arteriovenous malformation with fluctuating vision and ischemic central retinal vein occlusion and its sequelae: 25-year follow-up of a case.

A patient with a retinal arteriovenous malformation (AVM) had experienced episodic visual loss with spontaneous recovery for many years, followed by permanent visual loss secondary to central retinal vein occlusion. She subsequently progressed to development of retinal neovascularization extending onto the posterior vitreous face with recurrent vitreous hemorrhage requiring vitrectomy. A brief review of the literature is presented, and the cause of the fluctuations in vision and central retinal vein occlusion are discussed.

Adult↗

PubMed1994

Role of retinal pigment epithelium in the development of experimental autoimmune uveitis.

PURPOSE: To determine the role of retinal pigment epithelium in the induction of S-antigen-induced uveitis by administration of sodium iodate (NaIO3) to selectively damage the retinal pigment epithelium. METHODS: Forty-four Lewis rats were injected with 60 micrograms of S antigen in complete Freund's adjuvant. On postimmunization day 9 the rats were separated into four groups: three groups received NaIO3 at doses of 50, 25, and 10 mg/kg body weight, respectively, and the fourth group (control) received diluent. In addition, separate groups of animals (three in each group) received various doses of NaIO3 or diluent. All of the animals were killed on day 6 after NaIO3 injection, and the eyes were enucleated and submitted for light and electron microscopic examination. In addition, two groups of Lewis rats (6 in each group) were immunized with 0.5 ml of guinea pig spinal cord homogenate in complete Freund's adjuvant to induce experimental allergic encephalomyelitis. On postimmunization day 7, one group received NaIO3 at a dose of 50 mg/kg body weight, whereas the other group received diluent. All animals were killed between days 12 and 14, and spinal cord sections were obtained for microscopic examination. RESULTS: In the control group immunized with S antigen, severe (2+ to 4+) uveoretinitis developed in 70% of the animals. In contrast, only 18% of the animals injected with NaIO3 at a dose of 50 mg/kg body weight exhibited disease, and this was a mild (1+) form. The groups injected with 25 mg/kg (1+ to 2+) and with 10 mg/kg (2+ to 3+) of NaIO3 showed a mild to moderate degree of uveoretinitis in 27% and 50% of the animals, respectively. In the remainder of the animals there was no evidence of uveoretinitis. All of the NaIO3-treated animals showed selective necrosis of the retinal pigment epithelium; this was extensive in the higher dose group and focal in the lower dose groups. In the experimental allergic encephalomyelitis model there was no significant difference in incidence or histologic appearance of demyelinating disease in NaIO3- vs diluent-treated groups. CONCLUSIONS: These results indicate that the retinal pigment epithelium may play a role in the initiation and perpetuation of uveitis after sensitization with S antigen. The effect of NaIO3 appears to be localized to the retinal pigment epithelium; it had no effect on immune reactive cells, as evidenced by the development of experimental allergic encephalomyelitis in animals treated with NaIO3.

Animals↗

PubMed1990

[Effect of puberty on the development of diabetic microangiopathy].

Fluorescein angiography was used to follow the development of retinal microangiopathy at the time of puberty in 34 children with type I diabetes. When the results were compared with those for the control children who had suffered from the disease for a similar length of time, it was concluded that (in contrast with certain literature data) the process of sexual maturation does not essentially influence the development of retinal microangiopathy if the diabetes is maintained under good control for a long-lasting period. Appreciable roles in the rapid progression that is frequently observed in early adulthood are attributed to the sudden changes in the previously systematic living conditions (school, family, etc.).

Adolescent↗

PubMed2004

Neuropeptide Y and Y2-receptor are involved in development of diabetic retinopathy and retinal neovascularization.

BACKGROUND: Neuropeptide Y is a sympathetic neurotransmitter, a potent endothelium-derived angiogenic factor and a vascular mitogen. We have studied the role of the functional leucine7 to proline7 polymorphism of the signal peptide region of preproneuropeptide Y (prepro-NPY) as a genetic susceptibility factor for diabetic retinopathy. In addition, we investigated the role of the NPY Y2-receptor as a putative mediator of angiogenic NPY signaling in the retina. METHODS: Frequencies of proline7 (Pro7) carriers in the prepro-NPY were determined in type 1 and type 2 diabetes patients having retinopathy, in type 2 diabetes patients without retinopathy and in healthy control subjects. The role of Y2-receptor in hyperoxemia-induced retinal neovascularization was investigated in Y2-receptor knockout mice (Y2-/-) and in rats administered Y2-receptor mRNA antisense oligonucleotide. RESULTS: The carriers having Pro7 in the preproNPY are markedly over-represented among type 2 diabetes patients with retinopathy compared to type 2 diabetes patients without retinopathy and to the population control. Neonatal exposure to hyperoxia resulted in development of retinal neovascularization that was prevented in Y2(-1-) -mice, and significantly inhibited in rats treated with the Y2-receptor antisense oligonucleotide. CONCLUSIONS: NPY and Y2-receptor play important roles in diabetic retinopathy and retinal neovascularization and are thus potential new targets for drug molecules for treatment of retinopathy.

Adult↗

PubMed2001

Graded contribution of retinal maturation to the development of oxygen-induced retinopathy in rats.

PURPOSE: Newborn rats exposed to hyperoxia during the first days of life have been shown to exhibit not only vasculopathy but also permanent changes in the structure and function of the retina. Given that the rat retina is immature at birth and that the maturation process continues until the opening of the eyes at 14 days of life, this study was conducted to investigate the susceptibility of the retina to oxygen toxicity as a function of the degree of retinal maturity reached at the time of oxygen exposure. METHODS: Newborn rats were exposed to hyperoxia during selected postnatal day intervals. Scotopic electroretinograms were recorded at 30 and 60 days of age, and retinal histology was obtained at the end of the study. RESULTS: There was a strong correlation between the duration of the hyperoxic event and the structural and functional consequences in the retina. However, the repercussions were significantly more profound when the exposure to oxygen occurred within the second week of life (6-14 days), compared with earlier (0-6 days) or later periods (14-28 days). CONCLUSIONS: The results strongly suggest that the structural and functional retinal changes secondary to postnatal hyperoxia are not only the direct consequence of exposure to high levels of oxygen (i.e., free radicals), but also are determined by the level of retinal maturity reached at the time of oxygen exposure. The results also indicate that the structural anomalies precede the functional impairments.

Animals↗

PubMed2001

The role of basic helix-loop-helix genes in vertebrate retinogenesis.

The developing eye is a favorite model for the study of pattern formation and cell fate determination. Retinal neuron development, in particular, is an approachable system to study molecular and cellular aspects of cell determination and differentiation. Basic helix-loop-helix (bHLH) transcription factors are important regulators of retinal neurogenesis. Proneural bHLH genes have highly defined expression in the developing retina that are influenced by pattern formation and cell specification pathways. Each retinal cell class has unique bHLH requirements, implying that these genes regulate neuronal identity and function. Therefore, proneural genes represent a molecular focal point through which epithelial cells are transformed into a precise neural network. In this review, we focus on the bHLH factor Ath5, an important regulator of retinal ganglion cell development, and discuss factors that regulate its expression in the retina and the target genes through which it may confer specific neuronal properties.

Animals↗

PubMed1999

The development of the pattern of retinal ganglion cells in the chick retina: mechanisms that control differentiation.

Neurons in both vertebrate and invertebrate eyes are organized in regular arrays. Although much is known about the mechanisms involved in the formation of the regular arrays of neurons found in invertebrate eyes, much less is known about the mechanisms of formation of neuronal mosaics in the vertebrate eye. The purpose of these studies was to determine the cellular mechanisms that pattern the first neurons in vertebrate retina, the retinal ganglion cells. We have found that the ganglion cells in the chick retina develop as a patterned array that spreads from the central to peripheral retina as a wave front of differentiation. The onset of ganglion cell differentiation keeps pace with overall retinal growth; however, there is no clear cell cycle synchronization at the front of differentiation of the first ganglion cells. The differentiation of ganglion cells is not dependent on signals from previously formed ganglion cells, since isolation of the peripheral retina by as much as 400 microm from the front of ganglion cell differentiation does not prevent new ganglion cells from developing. Consistent with previous studies, blocking FGF receptor activation with a specific inhibitor to the FGFRs retards the movement of the front of ganglion cell differentiation, while application of exogenous FGF1 causes the precocious development of ganglion cells in peripheral retina. Our observations, taken together with those of previous studies, support a role for FGFs and FGF receptor activation in the initial development of retinal ganglion cells from the undifferentiated neuroepithelium peripheral to the expanding wave front of differentiation.

3T3 Cells↗

PubMed1995

Axonal target choice and dendritic development of ferret beta retinal ganglion cells.

We have investigated the relationship between axon targeting and dendritic morphology in beta retinal ganglion cells in the postnatal ferret. Axonal projections were assessed by making separate injections of different fluorescent retrograde tracers into either the superior colliculus or lateral geniculate nucleus in vivo. The dendritic morphology of retrogradely labelled cells was revealed by the in vitro intracellular injection of lucifer yellow in fixed retina. In this way, 405 retinal ganglion cells were triple- or double-labelled and characterized by their dendritic branching styles. Both the distinct dendritic morphology of beta cells and the characteristic restriction of their adult axonal terminals to the lateral geniculate nucleus emerge postnatally. Beta cell dendritic morphology is established between postnatal days 5 and 9. As in the cat (Ramoa et al., 1989), beta cells extend and then retract a projection to the superior colliculus as part of their normal development. Transient beta axonal collaterals to the superior colliculus persist beyond the period of cell death, but nearly all are withdrawn by postnatal day 15. No dendritically distinct beta cell projects to the superior colliculus alone, at any age. Heterochronic injections of different colours of retrograde tracer into the superior colliculus were used to study changes in the complement of the retinocollicular projection over time. A significant proportion of cells (58%) labelled at postnatal day 0 from the superior colliculus, which subsequently survived the period of cell death, were found to be beta cells that could no longer be demonstrated to have a retinocollicular axon.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

A sensitive and specific polymerase chain reaction-based assay for the diagnosis of cytomegalovirus retinitis.

PURPOSE: To develop a sensitive and specific laboratory assay for the diagnosis of cytomegalovirus retinitis. METHOD: We used a polymerase chain reaction-based assay for detection of cytomegalovirus DNA in vitreous samples. We attempted to detect cytomegalovirus DNA in 19 vitreous samples from patients with the acquired immunodeficiency syndrome (AIDS) who had untreated cytomegalovirus retinitis and in 40 vitreous samples from patients with AIDS who had been treated with systemic ganciclovir or foscarnet, or both. We also attempted to detect cytomegalovirus DNA in vitreous samples from 54 immunocompetent patients, including 32 with retinal detachment or macular hole, 11 with vitreous inflammation, and 11 with vitreous hemorrhage. Additionally, we attempted to detect cytomegalovirus DNA in 15 vitreous samples from patients with AIDS who had vitreoretinal inflammation not caused by cytomegalovirus. RESULTS: Cytomegalovirus DNA was detected in 18 of 19 eyes with untreated cytomegalovirus retinitis. We detected cytomegalovirus DNA in 19 of 40 vitreous samples from patients with previously treated cytomegalovirus retinitis. Cytomegalovirus DNA was not detected in any of 69 patients who did not have a clinical diagnosis of cytomegalovirus retinitis. Thus, the assay had an estimated sensitivity of 95% in detecting untreated cytomegalovirus retinitis and a sensitivity of 48% in detecting cytomegalovirus retinitis that had been treated with systemic ganciclovir or foscarnet, or both. The assay did not give false-positive results in patients with vitreous hemorrhage or vitreous inflammation. Most important, the assay did not give false-positive results in AIDS patients with vitreous inflammation from causes other than cytomegalovirus retinitis. CONCLUSION: We have developed a sensitive and specific diagnostic assay that will assist in the diagnosis of cytomegalovirus retinitis.

AIDS-Related Opportunistic Infections↗

PubMed1988

Development of neonatal mouse retinal neurons and photoreceptors in low density cell culture.

We describe here a culture method which allows the growth of dissociated mouse retinal neurons and photoreceptors in chemically defined medium. Neural retinas from 2-day-old C57/BL mice were dissected from other ocular tissues, including the pigment epithelium, and dissociated into a cell suspension after brief trypsination. Most cells attached as single, unaggregated units to substrata pretreated with polyornithine and the neurite-promoting factor (PNPF). The cells were cultured in serum-free, high pyruvate Dulbecco's modified Eagle's medium containing chemically defined supplements. Under these conditions, onset of cell process development was rapid, giving rise to extensive neurite networks. Three morphologically distinct cell types were apparent during the first week in vitro. Some cells retained a circular outline and failed to produce processes, while 50-60% of the cells developed as multipolar neurons showing a large cell body and several neurites. Approximately 90% of these cells reacted with an amacrine cell-specific monoclonal antibody. Some 30% of the cultured cells expressed phenotypic properties characteristic of rod photoreceptors, including a small cell body, an apical cilium, a short neurite with a spherule-like terminal body, and immunoreactivity with antibodies against opsin as well as a rod cell-specific monoclonal antibody. No further signs of outer segment differentiation were observed in these cells. Non-neuronal "flat" cells, which represented less than 0.5% of the total cell number, reacted with an antibody against the glial fibrillary acidic protein. The number of neurons and photoreceptors remained relatively stable during the first 4-7 days in vitro. During the second week in culture, however, there was specific degeneration of greater than 90% of the photoreceptor cells, while less than 20% of the multipolar neurons were similarly affected. Consequently, in addition to providing a system for studying the differentiation of retinal neurons and photoreceptors, the specific degeneration of photoreceptors in these mouse retinal cell cultures makes this system ideal for investigating factors influencing photoreceptor survival.

Animals↗

PubMed1990

Effects of visual or light deprivation on the morphology, and the elimination of the transient features during development, of type I retinal ganglion cells in hamsters.

Intracellular injection of Lucifer Yellow (LY) was used to study the detailed morphology of the normal visually deprived, and light-deprived superior colliculus projecting Type I retinal ganglion cells (RGCs) in hamsters. The soma size of the normal Type I cells ranged from 337 to 583 microns 2 with a mean of 436 microns 2. Two to six primary dendrites were observed in these cells. The mean dendritic field diameter was 495 microns and ranged from 309 to 702 microns. The dendritic field diameter of this population of cells exhibited an eccentricity dependence. Quantitative comparisons between the normal and visually deprived or light-deprived Type I RGCs indicated that the morphology of these three groups of cells were similar to each other in terms of the soma size, dendritic field diameter, branching pattern, and total length of the dendrites. During the normal development of cats and hamsters, several transient features, such as exuberant dendritic spines and intraretinal axonal branches, have been observed in the developing RGCs. The complete elimination of these transient features occurs at about 3 and 2 weeks after the opening of the eyes in cats and hamsters, respectively. In the present study, the hypothesis whether visual experience or light stimulation is required for the elimination of these transient features during development was examined. After studying a total of 115 mature Type I RGCs, which included cells from the normal, visually deprived and light deprived animals, no transient feature was observed. We conclude that visual or light deprivation has no effect on the morphological development of superior colliculus projecting Type I RGCs in hamsters, and the elimination of the transient features on the Type I RGCs during development does not depend on visual experience or light stimulation.

Animals↗

PubMed2001

[A rabbit model for human cytomegalovirus retinitis].

PURPOSE: To develop a rabbit model for human cytomegalovirus(HCMV) retinitis. METHODS: 0.1 ml of 1 x 10(6) plaque forming units/ml HCMV was injected into the vitreous cavity of 10 pigmented rabbit eyes. The eyes were examined ophthalmoscopically on days 1, 2, 3, 4 and 7 and once a week thereafter until 4 weeks after inoculation. Vitreal and retinal findings were graded from 0+ to 4+ on a scale of increasing severity. In addition, we examined the enucleated eyes 3 weeks after HCMV inoculation by histological and immunohistochemical techniques. RESULTS: All injected eyes developed vitreoretinal lesions. Vitreous opacities appeared the next day and increased until 4 days after HCMV inoculation. Whitish retinal exudates occurred on day 3 and increased until 3 weeks after HCMV inoculation. Vitreoretinal lesions then disappeared by 4 weeks after inoculation. Histological examination revealed intraretinal infiltration of inflammatory cells and disorganization of the inner retinal architecture. HCMV antigens were detected inside the retina by immunofluorescence using anti early protein antibody against HCMV. CONCLUSIONS: The results indicate that this rabbit model can be useful to develop and evaluate a new treatment modality for cytomegalovirus retinitis.

Animals↗

PubMed1999

Hypoxia inducible factor-1alpha is increased in ischemic retina: temporal and spatial correlation with VEGF expression.

PURPOSE: Hypoxia inducible factor-1 (HIF-1) is a transcription factor composed of HIF-1alpha and HIF-1beta subunits. HIF-1 transactivates multiple genes whose products play key roles in oxygen homeostasis, including vascular endothelial growth factor (VEGF). This study was designed to determine whether HIF-1 levels are increased in ischemic retina and whether there is a correlation with increased expression of VEGF. METHODS: C57BL/6J mice were killed at time points that span retinal vascular development (PO to adult), or on postnatal day (P) 7 they were placed in a 75% oxygen environment for 5 days and then removed to room air and killed after 0, 2, or 6, or 24 hours and 5 or 14 days. Eyes were frozen, and retinas were isolated and used for immunoblot analysis, or eyes were sectioned for immunohisto chemical staining for HIF-1alpha or HIF-1beta, or for in situ hybridization for VEGF. RESULTS: Immunoblots of retinal lysates showed low levels of HIF-1alpha at PO that were markedly increased at P4, remained high throughout the period of retinal vascular development and then decreased to an intermediate level in adults. HIF-1beta levels were relatively constant at all time points. In mice with oxygen-induced ischemic retinopathy, HIF-1alpha levels were increased in the retina. The peak of increase occurred at 2 hours, and levels returned to baseline by 24 hours. Immunohistochemistry showed increased staining for HIF-1alpha throughout the hypoxic inner retina, but not in the normoxic outer retina. There was no modulation of HIF-1beta levels. There was constitutive expression of VEGF mRNA in the inner nuclear layer that was increased 6 hours after the onset of hypoxia and remained elevated for several days. CONCLUSIONS: There are increased levels of HIF-1alpha in ischemic retina that show temporal and spatial correlation with increased expression of VEGF. These findings are consistent with the hypothesis that HIF-1 plays a role in upregulation of VEGF in ischemic retina.

Aging↗