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PubMed1996

Fate of DNA from retinal cells dying during development: uptake by microglia and macroglia (Müller cells).

The tunel technique of labelling fragmenting dna was used to examine cell death in the developing retina of the rabbit, rat and cat. TUNEL-labelled structures included the still-intact nuclei of retinal cells and smaller, strongly labelled bodies interpreted as fragments of disintegrating nuclei (apoptotic or pyknotic bodies). With confocal microscopy, the cytoplasm around labelled nuclei was observed to be labelled, suggesting that DNA fragments spread into the cytoplasm of the dying cell. Also observed were cells whose nuclei were TUNEL-but whose cytoplasm was TUNEL+, so that their morphology could be discerned. Evidence is presented that these are phagocytes, their cytoplasmic labelling resulting from the ingestion of the fragmenting DNA of a dying neighbour. Results suggest that in developing retina fragmenting DNA is phagocytosed principally by microglia and Müller cells, with a few neurones and no astrocytes active as phagocytes. In the postnatal material studied, microglia are the predominant phagocytes for cells dying in the ganglion cell and inner nuclear layers. Müller cells appear able to phagocytose cells dying in any retinal layer and, since microglia do not normally enter the outer nuclear layer, may be important for the phagocytosis of dying photoreceptors.

Animals↗
PubMed1993

Flexible open-loop anterior chamber intraocular lens implants.

PURPOSE: To determine the efficacy of flexible open-loop anterior chamber intraocular lens (AC IOL) implants in cataract surgery complicated by vitreous loss and in secondary implantation. METHOD: Results were reviewed in 18 eyes in the former group and in 43 eyes in the latter group that were operated on by the author over an 8-year period. RESULTS: Of 18 eyes in the former group, 13 (72%) had a final visual acuity of 20/40 or better. Cystoid macular edema was the most common cause of the decrease in visual acuity. Of 43 eyes in the latter group, 37 (86%) had a final vision equal to the best-corrected preoperative vision. A retinal complication developed in 6 of 18 eyes that received a primary AC IOL with vitreous loss, whereas no retinal complications developed in any of the 14 eyes that received a secondary AC IOL with vitreous loss (P = 0.021). For secondary AC IOL implantation, eyes with vitreous loss treated by Weck-cel sponge vitrectomy had the same visual results as eyes without vitreous loss. CONCLUSION: Flexible open-loop AC IOLs are safe and effective for primary implantation after vitreous loss and for secondary implantation.

Aged↗
PubMed2003

The outgrowth response of the axons of developing and regenerating rat retinal ganglion cells in vitro to neurotrophin treatment.

BDNF and NT-4 (but not NT-3 or CNTF) significantly enhanced the outgrowth of early embryonic and adult regenerating RGC axons when provided with a supportive substrate in vitro. BDNF and NT-4 treatment transiently increased RGC axon outgrowth from E15 rat retinas but not from retinas at older embryonic ages. The transient effect of BDNF and NT-4 and the inability of the neurotrophins to promote outgrowth from older embryonic retinal explants suggests a time frame of neurotrophin action and that other chemical factors (target-derived or otherwise) may be necessary for the continued maintenance of developing RGC axons. BDNF and NT-4 also enhanced the outgrowth of regenerating axons from adult retinal explants, but appeared to have a more subtle effect on axon outgrowth, in that the growth-promoting effects of BDNF and NT-4 appeared continuous throughout the incubation period. The suppression of RGC axon outgrowth from embryonic and adult retinae cultured in trkB-IgG-containing medium suggests that the response of developing and regenerating axons, to BDNF and NT-4 are likely to occur through trkB signalling.

Animals↗
PubMed1999

Astrocyte proliferation during development of the human retinal vasculature.

Wholemounts of human fetal retinas were labeled with antibodies to Ki67 or proliferating cell nuclear antigen, to map the distribution of proliferating cells in the developing primary vasculature and neural retina. Double labeling was used to determine the relative proportions of endothelial cells (CD34), astrocytes (glial fibrillary acidic protein - GFAP) and microglia (major histocompatability complex class II) associated with the developing vessels. The differentiated region of neural retina (cold spot) was 3.5 mm(2)at 15 weeks gestation (WG), centred on the incipient fovea, and increased in size with age to 80.5 mm(2)by 23-24 WG. Ki67 immunoreactive cells were distributed throughout the developing vasculature at all ages. The mean density of dividing cells in the neural retina increased with gestational age from 146 mm(-2)at 15 WG, to 624 mm(-2)at 23-24 WG. By 20 WG proliferation in the vasculature overlapped the margins of the cold spot, which was almost completely vascularized by 23-24 WG, except for a narrow strip on the horizontal meridian, which included the incipient fovea. Counts of CD34/Ki67 immunoreactive cells indicated that 15-52% of proliferations in the developing vasculature at 18 WG are endothelial cells. In contrast, in the fellow retina 65-85% cells were Ki67/GFAP immunoreactive, indicating proliferation of astrocytes in situ. No dividing microglia were observed. The findings suggest that large numbers of proliferating astrocytes accompany the developing vessels as they migrate across the primate retina.

Antigens, CD34↗
PubMed2000

Effects of neonatal exposure to cocaine in the development of the neurotransmitters retinal systems: an immunocytochemical and neurochemical study.

The visual system of rodents is affected if exposure to drugs, e.g., cocaine, occurs during prenatal or early postnatal development. This study aims to evaluate, in an experimental model of neonatal exposure to cocaine in the rat, the immunocytochemical expression of tyrosine hydroxylase in the retina and the levels of different neurotransmitters and its metabolites. Male Wistar rats were given 15 mg cocaine hydrochloride/kg body weight/day, subcutaneously, in two daily doses, from the day after birth (PND1) to PND6, 13, and 29. Controls were given 0.9% saline. Groups of rats were perfused at PND7, 14, and 30 with fixative, and the retinas were processed as wholemounts, and immunostained with the antibody anti-TH. Other groups were decapitated, and the retinas were dissected and processed by high performance liquid chromatography with electrochemical detection (HPLC-EC) for determination of dopamine and metabolites (DOPAC and HVA). A reduction in the retinal surface area was detected in the PND30 cocaine group, and a decrease in the density of the small TH-IR cells was found in the PND14 cocaine group although not reaching significant levels. The other quantitative parameters did not differ between the control and cocaine groups. The levels of neurotransmitters did not significantly differ between the groups at any age. These results show a differential vulnerability of the dopaminergic system of rats exposed neonatally to cocaine when compared with the effects found after prenatal exposure to the same drug.

Age Factors↗
PubMed2005

Retinopathy of prematurity: involution, factors predisposing to retinal detachment, and expected utility of preemptive surgical reintervention.

PURPOSE: To characterize involution of retinopathy of prematurity (ROP) following treatment at threshold, to identify findings during involution that portend development of retinal detachment, and to assess the potential utility of preemptive vitrectomy for eyes with high-risk features. METHODS: The probability of ROP involution and of retinal detachment evolution over time was analyzed in 262 treated eyes of 138 infants in a retrospective observational non-case controlled series. Expected utility of preemptive reintervention in eyes with high-risk features was evaluated using decision analysis. Modifications were devised to enhance classification of advanced ROP. RESULTS: ROP fully involuted in approximately 80% of eyes within 28 days of treatment. Vitreous organization meeting the study's clinically important definition was associated with a 31-fold (5.37 to 183.63; P < .0001) and a 13-fold (2.97 to 58.59; P < .0001) increase in the odds for retinal detachment for right and left eyes, respectively. Vitreous hemorrhage defined as clinically important was associated with a 38-fold (2.69 to 551.19; P = .007) and a 15-fold (1.65 to 144.12; P = .02) increase in the odds for retinal detachment for right and left eyes, respectively. As modeled, an expected utility of 0.85 was calculated for preemptive vitrectomy compared with 0.79 for deferred vitrectomy for eyes with clinically important vitreous organization. CONCLUSIONS: Acute-phase ROP involuted quickly in most eyes. Vitreous organization and vitreous hemorrhage were predictive of eyes that developed a retinal detachment. Decision analysis suggests that preemptive vitrectomy for eyes with vitreous organization meeting specific criteria is not likely to be worse than deferred vitrectomy, and it could be advantageous in some scenarios.

Decision Support Techniques↗
PubMed1996

Morphogenesis of retinal ganglion cells: a model of dendritic, mosaic, and foveal development.

Much is known about the morphological development of mammalian retinal ganglion cells. However, relatively little is understood about the mechanisms that direct dendritic development and determine ganglion cell morphology, mosaic organization, and foveal development. In the following, we review current data on primate retinal ganglion cell development and integrate it with information from other species into a general model of dendritic development. Furthermore, we propose that this model not only explains ganglion cell dendritic development, but also accounts for the establishment of retinal ganglion cell mosaics and the timing of foveal formation.

Animals↗
PubMed2001

Risk factors for cytomegalovirus retinitis following bone marrow transplantation from unrelated donors in patients with severe aplastic anemia or myelodysplasia.

Two cases of cytomegalovirus (CMV) retinitis following bone marrow transplantation (BMT) from unrelated donors are reported. 1 patient had been treated for severe aplastic anemia (SAA) and the other for hypoplastic myelodysplastic syndrome (MDS). Because first line therapy with antithymocyte globulin (ATG) and cyclosporin A (CsA) had failed, BMT was performed following a conditioning regimen of ATG, cyclophosphamide, and total lymphoid irradiation. Treatment for CMV retinitis was successfully carried out with gancyclovir (systemic and intraocular injection), foscarnet, and photocoagulation (Case 1) and gancyclovir and foscarnet (Case 2). Both patients also developed Epstein-Barr virus-associated lymphoproliferative disease (EBV-LPD). We compared these 2 cases with 14 SAA patients who did not develop CMV retinitis after BMT using marrow from either HLA-identical siblings (n = 9) or from unrelated donors (n = 5). Unlike the retinitis patients, the latter 5 patients received ATG only once. The retinitis patients had significantly lower CD4+ T-cell levels in their peripheral blood than the 14 patients who did not develop CMV retinitis. We believe that repeated treatment with ATG and transplantation from unrelated donors may lead to immune dysfunction that could increase the likelihood of CMV retinitis, as well as LPD. For such BMT patients, regular ophthalmic examinations and careful testing for CMV antigenemia are recommended.

Adolescent↗
PubMed1989

Retinal detachment after neodymium:YAG laser posterior capsulotomy.

We reviewed the records of 397 patients who had undergone Nd:YAG laser posterior capsulotomy between July 1983 and August 1988. Of the 366 eyes that had been followed up for three months or more, 13 (3.6%) developed a retinal detachment after capsulotomy; of these 13 detachments, 11 (84.6%) occurred within the first year. The combination of male gender with axial myopia (greater than or equal to 25.00 mm), a history of lattice degeneration, or a history of retinal detachment in the fellow eye was a significant risk factor for the development of retinal detachment after YAG capsulotomy.

Cataract Extraction↗
PubMed2004

Regression of retinopathy by squalamine in a mouse model.

The goal of this study was to determine whether an antiangiogenic agent, squalamine, given late during the evolution of oxygen-induced retinopathy (OIR) in the mouse, could improve retinal neovascularization. OIR was induced in neonatal C57BL6 mice and the neonates were treated s.c. with squalamine doses begun at various times after OIR induction. A system of retinal whole mounts and assessment of neovascular nuclei extending beyond the inner limiting membrane from animals reared under room air or OIR conditions and killed periodically from d 12 to 21 were used to assess retinopathy in squalamine-treated and untreated animals. OIR evolved after 75% oxygen exposure in neonatal mice with florid retinal neovascularization developing by d 14. Squalamine (single dose, 25 mg/kg s.c.) given on d 15 or 16, but not d 17, substantially improved retinal neovascularization in the mouse model of OIR. There was improvement seen in the degree of blood vessel tuft formation, blood vessel tortuosity, and central vasoconstriction with squalamine treatment at d 15 or 16. Single-dose squalamine at d 12 was effective at reducing subsequent development of retinal neovascularization at doses as low as 1 mg/kg. Squalamine is a very active inhibitor of OIR in mouse neonates at doses as low as 1 mg/kg given once. Further, squalamine given late in the course of OIR improves retinopathy by inducing regression of retinal neovessels and abrogating invasion of new vessels beyond the inner-limiting membrane of the retina.

Angiogenesis Inhibitors↗
PubMed2006

Glutamate regulates retinal progenitors cells proliferation during development.

The precise coordination of cell cycle exit and cell fate specification is essential for generating the correct proportion of retinal cell types during development. The decision to exit the cell cycle is regulated by intrinsic and extrinsic cues. There is growing evidence that neurotransmitters can regulate cell proliferation and cell fate specification during the early stages of CNS development prior to the formation of synaptic connections. We found that the excitatory neurotransmitter glutamate regulates retinal progenitor cell proliferation during embryonic development of the mouse. AMPA/kainate and N-methyl-d-aspartate receptors are expressed in embryonic retinal progenitor cells. Addition of exogenous glutamate leads to a dose-dependent decrease in cell proliferation without inducing cell death or activating the p53 pathway. Activation of AMPA/kainate receptors induced retinal progenitor cells to prematurely exit the cell cycle. Using a replication-incompetent retrovirus to follow the clonal expansion of individual retinal progenitor cells, it was observed that blockade of AMPA/kainate receptors increased the proportion of large clones, showing that modulation of endogenous glutamatergic activity can have long-term consequences on retinal cell proliferation. Real time reverse transcriptase-polymerase chain reaction and immunoblot analyses demonstrated that glutamate does not alter the levels of the mRNA and proteins that regulate the G1/S-phase transition. Instead, the activity of the Cdk2 kinase is reduced in the presence of glutamate. These data indicate that glutamate regulates retinal progenitor cell proliferation by post-translational modulation of cyclin/Cdk2 kinase activity.

Animals↗
PubMed1996

Secondary implantation of angle-supported anterior chamber and scleral-fixated posterior chamber intraocular lenses.

PURPOSE: To compare the results of secondary implantation of angle-supported anterior chamber intraocular lenses (IOLs) and scleral-fixated posterior chamber lenses. SETTING: Eye Clinic, University of Verona, Italy. METHODS: This study of 68 eyes of 60 patients comprised two groups. In Group A (n = 35), an angle-supported anterior chamber IOL was implanted and in Group B (n = 33), a scleral-fixated posterior chamber IOL. Follow-up was from 12 to 45 months. RESULTS: In Group A, one eye developed a retinal detachment and another, pseudophakic bullous keratopathy. In Group B, one eye had a major intraoperative choroidal hemorrhage and two developed a retinal detachment postoperatively. All other complications were minor. CONCLUSIONS: Although the rate of sight-threatening complications was about 6% for both groups, scleral-fixated posterior chamber IOLs were associated with more intraoperative and postoperative complications than angle-fixated anterior chamber IOLs, and surgery took longer. Thus, anterior chamber IOL implantation should be considered for older patients with relatively good endothelial cell counts.

Aged↗
PubMed2003

Incidence and management of cataract after retinal detachment repair with silicone oil in immune compromised patients with cytomegalovirus retinitis.

PURPOSE: To determine the incidence of and risk factors for cataract and to describe the visual outcomes of cataract surgery in eyes with cytomegalovirus-related retinal detachments repaired with silicone oil. STUDY DESIGN: Retrospective cohort study. METHODS: A prospectively generated database of all patients with cytomegalovirus retinitis examined at a single tertiary care institution was used to identify all cases of retinal detachment between October 1983 and August 1997. Data on retinal detachment repair, development of cataract, and outcomes of cataract surgery were obtained retrospectively. RESULTS: Among 904 eyes of 587 immune-compromised patients diagnosed with cytomegalovirus retinitis, 198 eyes of 155 patients developed retinal detachment. Among these, 106 eyes of 90 patients underwent retinal detachment repair with silicone oil. The Kaplan-Meier estimated median time to cataract was 1.8 months after surgery with silicone oil. The adjusted relative risk of cataract in eyes that underwent retinal detachment repair with silicone oil compared with eyes that did not was 6.74 (P <.0001). Eight of the eyes that developed cataract underwent uncomplicated cataract surgery by phacoemulsification and posterior chamber intraocular lens implantation. Among these, six eyes experienced >or=2 lines of improvement in visual acuity. All developed posterior capsule opacification a median of 7 days after cataract surgery. Four of five eyes that that underwent neodymium:yttrium-aluminum-garnet laser capsulotomy experienced >or=2 lines improvement in visual acuity. CONCLUSIONS: There is a high incidence of cataract after surgery with silicone oil tamponade for cytomegalovirus-related retinal detachment. Posterior capsule opacification occurs rapidly after cataract surgery in these patients.

AIDS-Related Opportunistic Infections↗
PubMed1998

Fibroblast growth factor receptor signaling in Xenopus retinal axon extension.

Fibroblast growth factor receptors (FGFRs) and N-cadherin both regulate axon extension in developing Xenopus retinal ganglion cells (RGCs). Cultured cerebellar neurons have been shown to require FGFR activity for N-cadherin-stimulated neurite outgrowth, raising the possibility that N-cadherin is a FGFR ligand. To investigate this possibility in the developing visual system, retinal neurons were transfected with a dominant-negative FGFR (XFD) and plated on purified N-cadherin substrates. XFD-expressing neurons extended markedly shorter processes than control GFP-expressing neurons, implicating a role for FGFRs in N-cadherin-stimulated neurite outgrowth. To examine whether N-cadherin and FGFRs share the same pathway or use distinct second messenger pathways, specific inhibitors of implicated signaling molecules were added to neurons stimulated by N-cadherin, basic fibroblast growth factor (bFGF), or brain-derived nerve factor (BDNF) (which stimulates RGC outgrowth by a FGFR-independent mechanism). Diacylglycerol (DAG) lipase and Ca2+/calmodulin kinase II inhibitors both significantly reduced outgrowth stimulated by N-cadherin or bFGF but not by BDNF. Furthermore, we show that inhibiting DAG lipase activity in RGC axons extending in vivo toward the optic tectum reversibly slows axon extension without collapsing their growth cones. Thus, a common second-messenger signaling pathway mediating both N-cadherin- and bFGF-stimulated neurite extension is consistent with a model in which N-cadherin directly modulates the FGFR or a model whereby both FGFR and N-cadherin regulate the same second-messenger system.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Cell fate specification in the developing Drosophila retina.

The developing Drosophila retina provides an excellent experimental system in which to address questions of cell fate choice and patterning. By focusing first on a detailed morphological description of eye development and more recently on the genes required for its development, the first steps have been taken toward understanding how these two aspects combine to direct cell fate in the retinal neuroepithelium. In addition, developing cell types emerge within the ommatidium in stereotyped patterns; these patterns may provide further clues regarding the mechanisms involved in cell fate choice. Previous reviews have focused on the detailed morphological description of, and molecules involved with, retinal development. This review focuses on current progress in understanding the role of several genes that play critical roles in retinal development, with special emphasis on how they define symmetric groups of cells within each ommatidium. In addition, the role of local cell interactions in directing cell fate is assessed.

Animals↗
PubMedDate not supplied

Retinal detachment in spondyloepiphyseal dysplasia congenita.

Retinal detachment is one of the most serious complications of spondyloepiphyseal dysplasia congenita (SEDC). The ocular complication of 12 patients with SEDC was studied. Three patients developed bilateral retinal detachments; five of the six detachments occurred during the period of rapid growth spurt. Our results suggest that patients with SEDC have an increased risk for development of retinal detachment during the period of rapid growth spurt.

Adolescent↗
PubMed2003

[Iatrogenic retinal breaks during vitrectomy: retrospective study].

PURPOSE: To establish the incidence and characteristics of iatrogenic retinal breaks occurring during vitrectomy and to propose a protocol for their management. METHODS: Retrospective study of 195 consecutive vitrectomies performed in 2001. Minimum follow up was 3 months for all cases. RESULTS: 13 patients with iatrogenic retinal breaks (6.6%) have been detected. In 8 cases the breaks affected the peripheral retina, in 4 cases they were located in the posterior pole and there was one retinal dialysis. In 4 cases there were more than one retinal break. 9 patients (70%) were vitrectomized for diabetic retinal complications. In 12 cases, the breaks were detected during surgery and treated with endolaser and/or cryoretinopexy (3 cases located inferiorly). Nevertheless 7 cases (54%) developed a retinal detachment, 2 of which could be reattached. CONCLUSIONS: Among iatrogenic retinal breaks produced during vitrectomy, the peripheral ones are slightly more frequent than the breaks in the posterior pole. Iatrogenic breaks occur more frequently in diabetic patients, having a bad prognosis and often developing a retinal detachment despite endolaser or cryoretinopexy.

Adult↗