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PubMedDate not supplied

Early identification of retinal subtypes in the developing, pre-laminated chick retina using the transcription factors Prox1, Lim1, Ap2alpha, Pax6, Isl1, Isl2, Lim3 and Chx10.

In this study, antibodies toward the transcription factors Prox1, Lim1, Ap2alpha, Pax6, Isl1, Isl2, Lim3 and Chx10 were used to identify and distinguish between developing cell types in the pre-laminated chick retina. The spatio-temporal expression patterns were analysed from embryonic day 3 (E3) to E9, thus covering a time-span from the onset of retinal cell-fate determination to when retinal laminas can be distinguished. Most transcription factors were found at early stages of development, enabling us to trace various precursor cell populations throughout the lamination process. With time, each transcription factor expression became restricted to distinct laminas or sub-laminas of the maturing retina. These early emerging patterns were compared and found to be consistent with those of the hatched chick retina, where the outer nuclear layer label for Lim3, Isl1 and Isl2. In the inner nuclear layer, horizontal cells labeled for Prox1, Lim1, Isl1, Ap2alpha and Pax6, bipolar cell labeled for Lim3, Isl1 and Chx10 and amacrine cells labeled for Ap2alpha, Isl1 and Pax6. The ganglion cell layer labeled for Isl1, Pax6 and Isl2. The immunolabeling patterns of Lim3 and Isl2 have not previously been described in detail.

Animals↗

PubMed1998

Distribution of mitochondria within Müller cells--II. Post-natal development of the rabbit retinal periphery in vivo and in vitro: dependence on oxygen supply.

The occurrence and localization of mitochondria within glial (Müller) cells and neurons of the peripheral (avascular) rabbit retina was studied electron microscopically and by immunocytochemical demonstration of the mitochondrial enzyme GABA transaminase (GABA-T). Post-natal development in vivo was compared with development of organ cultures from neonatal rabbit retinae, grown over 2 weeks in vitro. The adult pattern of mitochondrial localization (restriction to the sclerad end of the cells) was observed from the beginning of enzyme expression at early post-natal stages. However, when neonatal retinal pieces were grown in vitro with their vitread surface exposed to the air, their Müller cells contained mitochondria along most of their length. When functionally developed retinae from postnatal day 14 were explanted in vitro, they retained their sclerad mitochondrial distribution for almost 24 h but thereafter the inner portions of their cytoplasm became occupied by mitochondria within a few hours. This was achieved mainly by mitochondrial migration rather than by formation of new mitochondria because it was not prevented by cycloheximide-induced inhibition of protein synthesis. These data support the following hypotheses: (1) the mitochondrial distribution in Müller cells is determined by the local cytoplasmic O2 pressure (pO2), (2) existing mitochondria move towards cytoplasmic regions of sufficient pO2 by rather rapid migration and (3) the start of this migration is delayed by almost 24 h due to the action of as yet unknown control mechanisms. In contrast, the mitochondrial content of retinal ganglion and amacrine cells in the vitread retinal layers was virtually independent of the source and level of oxygen supply.

4-Aminobutyrate Transaminase↗

PubMed1992

The ocular manifestations of sickle-cell disease: a prevalence and natural history study.

Prophylactic photocoagulation may have a role in the treatment of proliferative sickle retinopathy in selected patients with SC disease, but none of the studies reported to date have established that such treatment of these eyes improves the long-term visual outcome as compared with the natural history as documented in this study. The similar visual outcomes in the eyes reviewed in this natural history study as compared with those that have been treated with photocoagulation should not be unexpected, because there is greater predilection for spontaneous involution or autoinfarction of the neovascular tissue in SC disease as opposed to the neovascularization that develops in other retinal vascular disease. A controlled, multicenter clinical trial designed to study those eyes at greatest risk should be considered. Such a trial should specify patient age (15 to 30 years), hemoglobin type (SC disease), and a minimum threshold of active proliferative disease (60 degrees or greater). Such criteria have been suggested by others. By comparing the outcome of eligible eyes randomly assigned to treatment or observation and followed for an extended period, it will be possible to learn whether laser photocoagulation offers a better prognosis than the natural history of proliferative sickle retinopathy. There is no question that in some eyes with proliferative sickle retinopathy, nonclearing vitreous hemorrhage and/or retinal detachment will develop. Clear definition of the risk factors leading to these advanced stages, however, is lacking, and the value of treatment is uncertain.

Adolescent↗

PubMed1995

Changes in adhesive force between the retina and the retinal pigment epithelium by laser photocoagulation in rabbits.

A closed eyeball model was designed to estimate the chorioretinal adhesion of the laser-photocoagulated region. We used it to measure the duration of development of retinal detachment during vitrectomy before and after killing the test rabbits. During testing, negative pressure was applied into the vitreous cavity of the pigmented rabbits. Laser burns were produced in the posterior retina by exposure to an argon blue-green laser beam with a focus diameter of 200 microns of 0.1 to 0.2 second duration and 150 to 250 mW intensity. One hour and one, two, five, seven and fourteen days following laser photocoagulation, vitrectomy was done with a cutting rate of 500 per minute, aspiration pressure of 50 mmHg and infusion pressure of 55.2 mmHg. After core vitrectomy, the rabbit was killed with an intravenous bolus of 100 mg sodium pentobarbital solution. After killing the rabbit, the vitreous cavity was continuously aspirated under the pressure of 25 mmHg while the infusion was stopped. The changes of the fundus, especially development of retinal detachment, were observed in the laser-treated and untreated regions before and after killing the rabbit. When retinal detachment was noted anywhere before killing the rabbit, this postmortem change was not observed. One hour following laser photocoagulation, the laser-treated retina was detached during core vitrectomy before killing the rabbit, and the untreated area was not detached. One day following photocoagulation, the retina was intact before killing the rabbit. After killing the rabbit, the laser-treated retina was detached in four minutes and the untreated retina in 18 minutes postmortem.(ABSTRACT TRUNCATED AT 250 WORDS)

Adhesiveness↗

PubMed1972

Incidence of ocular complications in patients undergoing renal transplantation.

The eyes of 39 patients who had received allogenic renal transplants were examined for signs of disease. Nine (23%) had early posterior subcapsular cataracts, two (5%) developed acute cytomegalovirus retinitis, and one developed steroid-induced glaucoma. The lesions which were found were all attributable to the immunosuppressive drug therapy. Thirty-five (87%) had detectable complement-fixing antibodies to cytomegalovirus.

Adolescent↗

PubMed1995

The range of PaO2 variation determines the severity of oxygen-induced retinopathy in newborn rats.

PURPOSE: This study was conducted to determine the potential influence of PaO2 fluctuation on the retinal neovascular response known to occur in newborn rats exposed to hyperoxic conditions. As an inherent corollary, the authors also defined the relationship between the fraction of inspired oxygen (FiO2) and the arterial blood oxygen tension (PaO2) in newborn rats. METHODS: Experiment 1 was composed of several oxygen-exposure protocols in which atmospheres of 10% oxygen concentration were alternated with different higher levels of ambient oxygen (50%, 40%, 30%, and room air). In experiment 2, two alternating oxygen concentrations were made to converge toward room air (20.9% oxygen) with each successive group of four treatment groups. These included another group exposed to alternating 50% and 10% oxygen, a group exposed to alternating 45% and 12.5% oxygen concentrations, one exposed to alternating concentrations of 40% and 15% oxygen, and a final group exposed to 35% and room air oxygen concentrations. In each case, oxygen was alternated between the two exposure concentrations every 24 hours. The term delta FiO2 is used to designate the difference in the two oxygen concentrations to which a treatment group was subjected, applying the units of fraction of inspired oxygen (i.e., delta FiO2 = 0.4 for the exposure to alternating 50% and 10% oxygen). At birth, litters of albino rats were placed in each of these environments for 13 or 14 days, after which PaO2 and retinal vascular development were assessed in some rats. The remainder were removed to room air for 4 days before the incidence and severity of abnormal neovascularization were measured. RESULTS: PaO2 and FiO2 were directly and linearly correlated (r2 = 0.998). In experiment 1, the extent of retinal vascular development on removal from oxygen was a linear function of delta FiO2. Retinal neovascularization subsequently occurred in all rats exposed to alternating 50% and 10% or 40% and 10% oxygen concentrations, but only a third of the 30% and 10% exposure group, indicating a minimum threshold for proliferative disease at delta FiO2 = 0.2. In experiment 2, retinal avascularity also increased linearly with increasing delta FiO2. There was a threshold for neovascularization between the exposure to alternating 45% and 12.5% oxygen and the 40% and 15% oxygen exposure (100% versus 4.8% incidence of neovascularization), indicating a requirement of < or = 12.5% oxygen episodes to stimulate a consistent proliferative response. CONCLUSIONS: These results suggest that PaO2 fluctuation and degree of hypoxia may have more influence on proliferative retinal disease in newborn rats than the extended hyperoxia that has historically received greater attention. Experimental designs that address the inherent differences in pulmonary function between intrinsically healthy animals and compromised premature infants are of substantial value to our understanding of the pathogenesis of retinopathy of prematurity.

Animals↗

PubMed2003

Retarded outer segment development in TrkB knockout mouse retina organ culture.

PURPOSE: To determine the effects of trkB deficiency in the mouse retina on photoreceptor development and retinal organization, in the absence of confounding systemic effects. METHODS: Newborn mice that carried two null trkB alleles (trkB-/-) and their wild type (WT) littermates were used for retinal organ cultures. On Day 21, rod development was assessed histologically in plastic sections (outer segment length) and retinal organization was analyzed using retinal cell-type specific antibodies. Anatomical data obtained from the organ cultures were compared to previously published histological results from in vivo data. RESULTS: (1) Rod outer segment length was significantly shorter in retinas from trkB-/- mice in the presence of normal numbers of rods. (2) No dopaminergic amacrine cells were observed in the knockout retina. (3) Unlike in the in vivo condition, recoverin-positive OFF-cone bipolar cells were present in trkB-/- retinas grown in culture. CONCLUSIONS: (1) These results demonstrate that rod outer segment development is compromised in the absence of trkB in the retina. (2) This study further supports our previous conclusion that the elimination of trkB expression alters rod development, because the presence of trkB receptors within the retina is essential for normal rod maturation and not because of confounding systemic effects. (3) More generally, this study stresses the importance of investigating complex phenotypes in gene knockout mice under conditions that isolate the organ under investigation from unrelated systemic variations.

Animals↗

PubMed1998

Transpupillary thermotherapy: results in 50 patients with choroidal melanoma.

OBJECTIVE: To evaluate the efficacy and safety of transpupillary thermotherapy in treating choroidal melanoma. METHODS AND PATIENTS: To perform transpupillary thermotherapy, infrared diode laser energy at 810 nm was used with a beam diameter of about 3 mm and 1-minute exposure time. All 50 patients had choroidal melanoma. We performed transpupillary thermotherapy in 21 tumors that had responded insufficiently to 800 Gy ruthenium 106 brachytherapy; it was combined with 800 Gy106Ru brachytherapy for 10 tumors greater than 5 mm in height and with 600 Gy for 19 tumors 5 mm or less in height. RESULTS: All but 1 tumor exhibited reduction in tumor height within a mean follow-up of 20.5 months (range, 6-49 months). In 41 eyes (82%), the tumor flattened completely. Visual acuity was 20/60 or better in 43 eyes (86%) before treatment and in 14 eyes (28%) at the last examination because of radiation vasculopathy. Neovascular glaucoma developed in 1 eye, and total retinal detachment developed in 2 eyes. Tumor recurrence was observed in 1 patient. CONCLUSIONS: Although long-term results are necessary to properly appraise this new therapy, transpupillary thermotherapy may be useful as a complementary modality to brachytherapy.

Adult↗

PubMedDate not supplied

Treatment of cytomegalovirus retinitis with DHPG in a patient with AIDS.

A 31-year-old homosexual man with AIDS, bilateral cytomegalovirus (CMV) retinitis and optic neuritis in one eye, was treated with DHPG. The drug is an acyclic nucleoside analogue of guanosine with antiviral activity. The visual acuity at the start of treatment was R.E.: no light perception and L.E.: 1.25. There was bilateral regression of retinal exudates on DHPG 5 mg/kg twice a day during 2 weeks. The visual result however was poor because of the optic nerve involvement, which did not improve during DHPG treatment. Four weeks later there was a recurrence of retinitis with the development of exudative retinal detachment in the eye with optic neuritis, despite maintenance therapy of 5 mg/kg once a day Monday through Friday. The dose was increased to 5 mg/kg twice a day, but after 1 week treatment had to be discontinued because of neutropenia. Eight days later treatment was restarted with DHPG 5 mg/kg in a single daily dose during 17 days, which led to remission of retinitis but retinal reattachment did not occur. Thereafter maintenance therapy was continued. Visual acuity remained unchanged. DHPG appears to be effective in treating cytomegalovirus retinitis but long-term suppressive therapy would be necessary to prevent recurrence of the retinitis.

Acquired Immunodeficiency Syndrome↗

PubMed2002

IGF-I is critical for normal vascularization of the human retina.

Experimental and clinical studies suggest that GH and IGF-I may be involved in neovascularization of the retina in diabetes and retinopathy of prematurity. However, the role of GH and IGF-I has not been well established in normal retinal vessel development in humans. Therefore, we examined retinal vessel morphology by digital image analysis of ocular fundus photographs in 13 patients with genetic defects of the GH/IGF-I axis and low levels of IGF-I during and after normal retinal vessel growth. Eleven patients (four females and seven males aged 10-49 yr) had defects of the GH receptor (Laron syndrome). One male (20 yr) had a partial deletion of the IGF-I gene, and one female (14 yr) had a single allele deletion of the IGF-I receptor gene. Patients with defects in the GH/IGF-I axis had significantly less retinal vascularization as evidenced by lower number of vascular branching points (median 23, range 16-25), compared with the reference group of 100 normal controls (median 28, range 19-40, P < 0.001). All 13 individuals had vascular branching points below the median of the reference group. This is the first study to provide genetic evidence for a role of the GH and IGF-I system in retinal vascularization in humans.

Adolescent↗

PubMed1989

Extracellular matrix alterations precede vascularization of the retinal pigment epithelium in dystrophic rats.

In Royal College of Surgeons (RCS) rats, the defective retinal pigment epithelium (RPE) fails to phagocytose the shed outer segment membranes, and the photoreceptors degenerate. Following degeneration of the photoreceptors, neovascularization and vitreo-retinal membranes (VRMs) develop. Blood-retinal barrier abnormalities at the level of the RPE suggested that Bruch's membrane extracellular matrix filtration barriers might also be abnormal. To study the progression of RPE cell, extracellular matrix and vascular alterations in the dystrophic retina, we used the cationic tracer polyethyleneimine and electron microscope morphometric techniques. At two weeks in the RCS retina, the RPE and retinal vessels, and their basal laminae, appeared normal. By two months, the RPE was hypertrophic and duplicated in some areas, and flattened in others. The RPE basal lamina was thickened (171% of the control, p less than .01), and there were more anionic sites along the RPE basal surface (158% of the control, p less than .01). Patches of displaced basal lamina material appeared within the RPE basal infoldings. By four months and later numerous retinal vessels were present within the RPE layer. In addition, cords of migrating RPE cells surrounded presumptive new vessels branching from the RPE layer towards the inner limiting membrane. The RPE-associated vessels exhibited diaphragmed fenestrae and channels, unlike normal retinal vessels, and their basal laminae were marked by anionic sites. These observations of RPE and extracellular matrix changes prior to vascular proliferation, and VRM formation in the dystrophic retina suggest that the RPE-associated extracellular matrix changes may contribute to vascular alterations in the dystrophic retina. A preliminary report of these findings has been presented previously.

Aging↗

PubMed2003

Drosophila retinal homeobox (drx) is not required for establishment of the visual system, but is required for brain and clypeus development.

The possibility that mechanisms of retinal determination may be similar between vertebrates and Drosophila has been supported by the observations that Pax6/eyeless genes are necessary and sufficient for retinal development. These studies suggest that the function of other gene families, operating during early eye development, might also be conserved. One candidate is the retinal homeobox (Rx) family of transcription factors. Vertebrate Rx is expressed in the prospective eye and forebrain and is required for eye morphogenesis, retinal precursor appearance, and normal forebrain development, indicating that it is an essential regulator of early eye and brain formation. Here, we test the hypothesis that Drosophila Rx (drx) is required for adult and larval eye development. We have isolated a drx null allele and demonstrate that the mutant compound eye and larval visual system is not detectably abnormal. However, we find that drx is required for development of a central brain structure, the ellipsoid body, suggesting that Rx function in the brain may be conserved. Finally, we characterize a novel anterior head phenotype and demonstrate that drx is required for clypeus development. Thus, our data suggest that drx may be required for the regulation of genes involved in brain morphogenesis and clypeus precursor development. We propose that differences in insect and vertebrate eye development may be explained by changes in gene regulation and/or the tissue of origin for eye precursor cells.

Alleles↗

PubMed2003

Acute retinal necrosis following epidural steroid injections.

PURPOSE: To report a side effect of epidural corticosteroid injections for back pain. DESIGN: Case series. METHODS: Review of clinical charts and photographs. SETTING: Private retina practice. RESULTS: Two patients developed acute retinal necrosis syndrome following epidural corticosteroid injections for back pain. Referral was delayed in one patient. One patient developed bilateral secondary rhegmatogenous retinal detachment, and both developed secondary macular pucker. CONCLUSIONS: Acute retinal necrosis can follow epidural corticosteroid injections. Patients should be warned about this possibility and advised to report should photopsias, photosensitivity, blurred vision, or new floaters develop after treatment. Orthopedists should be aware of the complication and promptly refer patients with symptoms for dilated fundus examination by an ophthalmologist.

Acyclovir↗

PubMed2001

Ischemic maculopathy in patients with acquired immunodeficiency syndrome.

PURPOSE: To describe the characteristics of ischemic maculopathy in patients with human immunodeficiency virus (HIV) infection, as a means of understanding this uncommon disorder more fully. METHODS: This is a multicenter, retrospective review of clinical data available for five HIV-infected patients who were given the diagnosis of ischemic maculopathy. RESULTS: All cases had been diagnosed on the basis of fluorescein angiograms obtained after patients complained of vision loss. Four of the five patients had bilateral macular disease. Visual acuity at presentation in the nine affected eyes ranged from 20/20 to count fingers. Vision loss was gradual in both eyes of one patient and was abrupt in onset in seven eyes. Each of the seven eyes with abrupt vision loss had opacification of the superficial retina and/or intraretinal hemorrhages near the fovea. Fluorescein angiography revealed enlargement of the foveal avascular zone and mild staining of the juxtafoveal vessels in affected eyes. Six eyes had active or clinically inactive cytomegalovirus retinitis at presentation, and a seventh eye developed cytomegalovirus retinitis 2 weeks later. All patients were receiving anticytomegalovirus drugs when they developed visual symptoms. Visual acuity remained stable in five eyes, became worse in two eyes, and improved in two eyes; final visual acuity ranged from 20/25 to count fingers. CONCLUSIONS: Ischemic maculopathy may cause profound and permanent vision loss in HIV-infected individuals. Fluorescein angiography should be considered in all HIV-infected patients with unexplained loss of vision. The pathogenesis of ischemic maculopathy remains unknown.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Failure of a prospective trial to detect cytomegalovirus retinitis after initiation of highly active antiretroviral therapy.

Thirty-one patients with AIDS with CD4+ T-cell counts of less than 75/mm3 were enrolled in a prospective study to determine the incidence of cytomegalovirus (CMV) retinitis and changes in CD4+ T-cell counts and viral loads following initiation of highly active anti-retroviral therapy (HAART). Patients were assessed using an Amsler grid, a visual field test, a questionnaire, and direct and indirect funduscopy. Only one patient developed an opportunistic infection, and the majority of patients had a threefold decrease in their viral loads and an increase in CD4+ T-cell counts within 2 months of initiating HAART. These findings support the belief that recent therapies modify the natural history of HIV infection and that new clinical approaches will be needed to address the changing profile of HIV/AIDS patients. None of our patients developed CMV retinitis. The findings add to those of other researchers, and suggest that if CMV retinitis does develop after HAART, it is an unusual finding that may be due to preexisting, subclinical retinitis rather than failure of HAART to reconstitute full immune cell recovery.

AIDS-Related Opportunistic Infections↗

PubMed2005

Angiopoietin 1 prevents retinal detachment in an aggressive model of proliferative retinopathy, but has no effect on established neovascularization.

Vascular endothelial growth factor (VEGF) plays a central role in vasoproliferative diseases in the retina, however, other gene products modulate its effects. The angiopoietins are particularly important in this regard. Angiopoietin 2 (Ang2) collaborates with VEGF to stimulate neovascularization (NV) in some situations, but in other situations causes regression of NV. Ang2 also causes a transient increase in vascular density during retinal vascular development. In this study, we sought to determine if Ang1 has similar activities. The effects of Ang1 were tested in double transgenic mice with inducible expression of Ang1. Increased expression of Ang1 in the retina during retinal vascular development did not cause a detectable alteration in vascular density. Also, unlike Ang2, increased expression of Ang1 had no effect on established retinal or choroidal NV. However, when Ang1 expression was initiated simultaneously with that of VEGF, it strongly suppressed VEGF-induced NV and prevented retinal detachment. These data indicate that the timing of Ang1 expression is a critical determinate of its effects on VEGF-induced NV in the retina; it effectively blocks the initiation and progression of NV, but cannot reverse established NV or reduce leakage from NV. These data suggest that increased expression of Ang1 may be a good strategy for prophylaxis of retinal NV, but is unlikely to be effective as monotherapy of established NV.

Angiopoietin-1↗

PubMed2004

[Peripheral retinal degenerations--treatment recommendations].

This report reviews the clinical appearance of degenerative diseases of the peripheral retina in relationship to the risk of developing a rhegmatogenous retinal detachment. We present recommendations for preventive treatment in eyes at increased risk of developing retinal detachment. Retinal degenerations are common lesions involving the peripheral retina but most of them are clinically insignificant. Lattice degeneration, degenerative retinoschisis, cystic retinal tufts, and very rarely zonular traction tufts can result in rhegmatogenous retinal detachment. Therefore, these lesions have been considered for prophylactic treatment; however, adequate studies have not been performed to date. Most of the peripheral retinal degenerations may not require treatment except in rare, high-risk situations. According to current knowledge there is no higher incidence of secondary pucker or other side effects after laser coagulation. Therefore, generous laser indication is recommended if risk factors apply.

Cryosurgery↗

PubMed2000

Effect of perifoveal tissue dissection in the management of acute idiopathic full-thickness macular holes.

OBJECTIVE: To evaluate the efficacy of perifoveal tissue dissection (PTD) on patients undergoing pars plana vitrectomy for idiopathic macular holes of less than 1-year's duration. METHODS: Pars plana core vitrectomy was performed on 107 eyes of 104 consecutive patients with acute idiopathic macular holes. One cohort had routine PTD. In the other cohort, no attempt was made to strip preretinal tissue. Follow-up was longer than 6 months (follow-up range, 6 to 36 months). RESULTS: Overall, 95 (89%) of all macular holes were closed. Visual acuity improved 2 lines or more of the Snellen letter chart in 91 eyes (85%). A postoperative visual acuity of 20/50 or better was achieved in 79 eyes (74%). A transient increase in intraocular pressure (230 mm Hg) developed in 25 eyes (23.4%). In 6 eyes (5.6%) a retinal detachment developed. One eye had retinal pigment epithelial changes and 1 patient reported peripheral field loss. No statistically significant differences were noted between eyes having PTD and those without PTD for any outcome measure. CONCLUSION: In this series, no beneficial or adverse effect could be demonstrated by performing PTD in eyes undergoing pars plana core vitrectomy for acute idiopathic macular holes.

Acute Disease↗