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PubMed2006

Pea3 expression is regulated by FGF signaling in developing retina.

FGF signaling has been implicated as an important regulator of retinal development. As a first step in characterizing potential downstream targets of FGF signaling in the retina, we have analyzed expression of Pea3, a member of the Pea3 class of Ets-domain transcription factors, in the developing eye. We find that Pea3 is expressed in the developing retina, and its transcription is regulated by FGF receptor activation. In addition, FGF signaling activates Cath5, a gene necessary for retinal ganglion cell differentiation. These results suggest that FGF signaling via MAPK up-regulates transcription factors that in turn control retinal ganglion cell differentiation.

Animals↗

PubMed2006

Role of the calcium modulated cyclases in the development of the retinal projections.

Transmembrane isoforms of adenylate cyclases (AC) integrate a wide variety of extracellular signals from neurotransmitters to morphogens and can also regulate cAMP production in response to calcium entry. Based on observations in the barrelless mouse strain, the Adcy1 gene (AC1) was involved in the segregation of binocular retinal inputs. To determine the potential role of other AC isoforms we localized the Adcy genes in the visual centres during development, using in situ hybridization. Six different AC subtypes were found in the developing retinal ganglion cell layer (RGC; AC1, AC2, AC3, AC5, AC8, and AC9), and three AC subtypes were expressed in the central brain targets, the dorsal lateral geniculate nucleus (AC1 and AC8), the ventral lateral geniculate nucleus (AC2 and AC8) and the superior colliculus (AC1, AC2, AC8). Using a genetic approach we tested the role of the calcium modulated cyclases AC1, AC5 and AC8 for the segregation retinal fibres. Ipsilateral retinal axons remained exuberant in the AC1(-/-) mice, with overlapping retinal projections from both eyes in the superior colliculus and the visual thalamus. These abnormalities were similar to those of barrelless mouse mutants. No abnormalities were detectable in the AC5(-/-) or the AC8(-/-) mice. Similar abnormalities were noted in the single AC1(-/-) and the AC1/AC8 double-knockout mice (DKO). Thus, only AC1 is required for the maturation of the retinal axon terminals whereas AC5 and AC8 are not needed. The specificity of AC1's action is linked to its cellular localization in the RGCs and to its distinctive functional profile, compared with the other cyclases expressed in the same cells.

Adenylyl Cyclases↗

PubMed1975

Retinal detachment after strabismus surgery.

Four nonmyopic eyes in three patients developed retinal detachment after strabismus surgery. Certain features common in all four eyes included the presence of a chorioretinal scar corresponding in location to the muscle operated on, proliferating fibrous tissue adjacent to the scar, and varying degrees of vitreous hemorrhage. These findings were similar to those in retinal detachments after perforation of the eye by foreign bodies. Penetration of the globe by the needle during muscle surgery was considered the etiologic factor. The use of spatula needles to prevent piercing of the globe is suggested, and in case such accident is suspected, diathermy or cryoapplication over the perforation site is advised.

Adult↗

PubMed1978

Ocular retardation (or) in the mouse.

The ocular retardation (or) mutation in mice has been studied morphologically in serial 1 mu sections. This recessively inherited, fully penetrant mutation is characterized by an early arrest of retinal development, aplasia of the optic nerve, cataractous degeneration of the lens, and microphthalmia. We describe early alterations of normally occurring morphogenetic cell death in the optic cup and aberrations of optic fissure formation which appear to precede the arrest of retinal and optic nerve development. The subsequent disappearance of central retinal vessels and cataract formation are interpreted as secondary phenomena.

Animals↗

PubMed1998

GABA as a developmental signal in the inner retina and optic nerve.

Gamma-aminobutyric acid (GABA) acts as an inhibitory neurotransmitter in the mature vertebrate retina, where it is localized predominantly in amacrine cells, and to a lesser extent in other cell types. During development, GABA is expressed transiently in additional cells, including retinal ganglion cells and horizontal cells. Elements of the GABA system, including GABA uptake and release mechanisms and GABA receptors, are also expressed early in retinal development, well in advance of the onset of visual function. The GABA transporter is a major component of the GABA system in the mature retina, and is most likely responsible for GABA release early in development, prior to the establishment of vesicular synaptic transmission. GABA, produced by amacrine cells and retinal ganglion cells, may serve a developmental role in the establishment of circuitry in the retinal inner plexiform layer and may also be involved in the formation of appropriate central connections by retinal ganglion cell axons.

Animals↗

PubMed2006

Development of inner retinal function, evidenced by the pattern electroretinogram, in the rat.

Though the rat is increasingly used as an animal model in ophthalmic research, including the study of glaucoma, little is known about age-related changes in its inner retinal function. The aim of this study was to evaluate these changes in the rat during the first 18 weeks of life. The pattern electroretinogram (PERG) was used to monitor inner retinal activity in 16 developing rats. In each animal, recordings were conducted at ages 3, 5, 7, 11, 14 and 18 weeks to assess age-related changes in function. Signals were evoked by five stimuli of progressively increasing check width (subtending 82-1312 arc minutes of visual angle) that were projected directly onto the fundus through a specially modified ophthalmoscope which allowed visual and manual control of stimulus quality. Poor signal:noise ratio prevented signal analysis at age 3 weeks. Subsequently, PERG amplitude increased significantly, up to 242% (depending on stimulus check width), during weeks 5-11. After peaking at 11 weeks, signal amplitude declined moderately. Signal latency mirrored that of amplitude, decreasing during the first 11 weeks, and then increasing steadily. Latency was not affected by stimulus check width. Age was highly correlated with P1 latency (R(2)=0.80) and moderately correlated with N2 latency (R(2)=0.52). Therefore, we propose that studies of inner retinal diseases (such as glaucoma) in the rat model should use age-matched controls, as electrophysiological results may be confounded by age-related changes. The rat PERG undergoes many of the age-related changes that have been reported in humans, and thus may serve as an animal model to study development of inner retinal function.

Aging↗

PubMed2003

Two zebrafish mutants, ebony and ivory, uncover benefits of neighborhood on photoreceptor survival.

Zebrafish offer a tractable system for the study of retinal development and degeneration, to provide insights into human retinal degeneration. We have begun to dissect the question of neighborhood effects on photoreceptor differentiation and survival through the isolation and characterization of mutants with retinal degeneration. We describe two mutants, ebony and ivory, isolated through a behavioral screen for blind mutants induced by ethyl nitrosourea mutagenesis. Chimeric analysis was conducted to attempt to rescue the photoreceptor degeneration. In ebony, the photoreceptor cell death was both cell autonomous and nonautonomous in nature, whilst the photoreceptor cell death was strikingly nonautonomous in ivory. The rescue at a distance is in keeping with a putative diffusible survival factor. We propose a density-dependent nonautonomous neighborhood effect to explain these findings.

Alkylating Agents↗

PubMed2005

First experiences with high-density silicone oil (Densiron) as an intraocular tamponade in complex retinal detachment.

BACKGROUND: In this study, we evaluated the anatomic and functional outcome and intraocular adverse effects after a 3-month endotamponade with Densiron 68, a mixture of F(6)H(8) with silicone oil, in complex inferior re-detachments. METHODS: Forty-eight eyes of 48 patients aged 27-82 years with retinal re-detachment due to proliferative vitreoretinopathy (PVR) grades CP1 to CA7 were included. Mean duration of the Densiron endotamponade was 108.7+/-66.9 days, with a mean follow-up after removal of 102.8+/-31.9 days. RESULTS: Twenty-two patients (45.8%) showed stable retinal reattachment after Densiron removal. Fourteen patients (29.2%) developed retinal re-detachment after removal, generally within 1 month and in the upper circumference (n=8). In 11 patients (22.9%) recurrent re-detachment (inferior n=8) appeared during Densiron endotamponade. In one eye (2.1%) treatment was primarily unsuccessful. Visual acuity improved from mean logMAR 1.66+/-1.03 to 1.47+/-0.97 (not statistically significant, P=0.257). Side effects included temporary inflammatory reaction (n=10), fibrin accumulation (n=6), sterile hypopyon (n=2), vitreous hemorrhage (n=6), elevated IOP (n=5), emulsification (n=4) and chronic hypotony (n=4). CONCLUSION: The anatomical success rate without further interventions of 45.8% (22 of 48 patients) seems unsatisfactory. However, in evaluating the potential of Densiron, it should be considered that all patients in this study had previous surgery with standard procedures, including silicone oil, which had already failed. Intraoperative laser photocoagulation of the periphery of the upper quadrants might reduce the risk of retinal re-detachments.

Adult↗

PubMed1992

Retinopathy of prematurity.

ROP is a common disorder among extremely low-birth-weight premature infant survivors and may cause total vision loss in as many as 2% to 4% of those weighing less than 2 lb (1 kg) at birth. Regular examinations begun in the intensive care unit permit early detection and treatment of progressive ROP, reducing visual impairment. Ongoing research into antioxidants, angiogenesis, light exposure, and newer surgical techniques may offer new approaches for preventing and treating established ROP. Infants who have had ROP that regressed should continue regular ophthalmologic follow-up to detect and treat myopia, strabismus, and if they have cicatricial sequelae, late retinal detachments as teens or adults. Infants who develop retinal detachments should be referred for early intervention and special education programs and remain in regular ophthalmologic follow-up for the detection and treatment of further ophthalmic complications.

Humans↗

PubMed1990

Ontogenesis of the electroretinogram in a precocial mammal, the guinea pig (Cavia porcellus).

1. Ontogenesis of the electroretinogram, the mass electrical response of the retina to flash light stimuli, was studied in the guinea pig (Cavia porcellus), a precocial species with visual function at birth. 2. a-Wave components, b-wave, oscillatory potentials, slow PIII, and c-wave responses to flash stimuli developed between 55 and 64 days of gestation (full term is 68-69 days). 3. a-Waves attributable to photoreceptor functions were fully mature at 60 days. 4. ERG development lagged behind the reported critical milestones in retinal development; its prenatal onset indicates that no history of light entrainment is required for initiation of a mature ERG response.

Aging↗

PubMed1993

Experimental long-term vitreous replacement with purified and nonpurified perfluorodecalin.

Highly purified perfluorodecalin and non-purified perfluorodecalin were injected into 34 rabbit eyes after mechanical vitrectomy, to evaluate the retinal tolerance in long-term vitreous replacement and the effect of purification on the retina. Unpurified perfluorodecalin caused severe inflammation and retinal damage and eight of ten eyes had developed retinal detachment after four weeks. In the eyes injected with highly purified perfluorodecalin, we observed retinal changes of the rod and cone, outer nuclear, and ganglion-cell layers after two weeks, which progressed to a thinning of all layers of the retina by the fourth week and to localized areas of retinal atrophy by the eighth week in the lower part of the eyes. Retinal damage in the upper part occurred after four weeks. At the perfluorocarbon-aqueous interface we observed a band of retinal necrosis that was noticed in all eyes four weeks postoperatively regardless of the substance used.

Animals↗

PubMed2004

Emergence of drug-resistant cytomegalovirus retinitis in the contralateral eyes of patients with AIDS treated with ganciclovir.

The purpose of the present study was to examine the emergence of ganciclovir-resistant virus in the contralateral eyes of patients who received treatment for cytomegalovirus retinitis with either a ganciclovir implant plus oral placebo, a ganciclovir implant plus oral ganciclovir, or intravenous (iv) ganciclovir. Viral DNA was amplified from vitreous specimens and was assayed for UL97 and UL54 resistance mutations. Resistant viral genotypes were found in the contralateral eyes of 0 of 28 patients treated with a ganciclovir implant plus oral placebo, in 5 of 23 patients treated with a ganciclovir implant plus oral ganciclovir, and in 1 of 6 patients treated with iv ganciclovir. All resistance mutations were in codons 591, 592, or 594 of the UL97 gene. Treatment of unilateral cytomegalovirus retinitis with systemic ganciclovir decreases the risk of development of secondary sites of infection, but, in contralateral eyes that develop retinitis, this approach to treatment is associated with a higher prevalence of drug resistance, compared with treatment with the ganciclovir implant alone (P=.023; Fisher's exact test).

AIDS-Related Opportunistic Infections↗

PubMed1991

Retinal detachment after YAG-laser capsulotomy.

Preoperative findings and postoperative results in 8 patients with retinal detachment after YAG-laser capsulotomy are described. In this period the over-all incidence of clinical retinal detachment in pseudophakic eyes after YAG capsulotomy in our hospital was 1.0% (2 of 193). Possible relationships between YAG-laser capsulotomy and retinal detachment are discussed. Two risk factors for developing retinal detachment were found in 6 of 8 patients. After surgical repair 7 retinas were re-attached. The final visual acuity was better than 0.5 in 5 patients.

Aged↗

PubMed1991

Acute retinal necrosis syndrome.

Acute retinal necrosis (ARN) is a rare syndrome with characteristic fundal appearances which can have devastating effects on vision. We present six cases (nine eyes) seen in the Medical Eye Unit of St Thomas's Hospital over the past six years and discuss the clinical features, aetiology, and management. Our findings support the present consensus that the condition is caused by varicella zoster virus (VZV) or herpes simplex virus (HSV). One of our patients, who was atypical in having common variable hypogammaglobulinaemia, had suffered a widespread zosteriform rash immediately prior to the onset of ARN, while another had suffered a herpes simplex uveomeningoencephalitis. All cases had characteristic confluent peripheral retinal necrosis, and three of the nine eyes developed retinal detachment. Retinal arteritis was a prominent and helpful diagnostic feature in one case. From combining all reports to date of this rare condition it is possible to conclude that ARN is unilateral in 65% of cases.

Adult↗

PubMed2001

Onset and time course of apoptosis in the developing zebrafish retina.

In mammalian development, apoptosis spreads over the retina in consecutive waves and induces a remarkable amount of cell loss. No evidence for such consecutive waves has been revealed in the fish retina so far. As the zebrafish is of growing importance as a model for retinal development and for degenerative retinal diseases, we examined the onset and time course of apoptosis in the developing zebrafish retina and in adult fish. We found that apoptosis peaked in the ganglion cell layer (GCL) and inner nuclear layer (INL) in early developmental stages (3-4 days post-fertilization; dpf) followed by a second, but clearly smaller wave at 6-7dpf. Apoptosis in the outer nuclear layer (ONL) started at 5dpf and peaked at 7dpf. This late-onset high peak of apoptosis of photoreceptors is different from that of all other species examined to date. With 1.09% of cells in the GCL and 1.10% in the ONL being apoptotic, the rate of apoptosis in the developing zebrafish retina was conspicuously lower than that observed in other vertebrates (up to 50% in GCL). During development (2-21dpf), apoptotic waves were most obvious in the central retina, whereas in the periphery near the marginal zone (MZ), apoptosis was much lower; in adult animals, practically no apoptosis was present in the central retina but it still occurred near the MZ. Our data show that the onset and time course of apoptosis in the GCL and INL of the zebrafish is comparable with other vertebrates; however, the amount of apoptosis is clearly reduced. Thus, apoptosis in the zebrafish retina may serve more as a mechanism for the fine tuning of the retinal neuronal network after mitotic waves during development or in remaining mitotic areas than as a mechanism for eliminating large numbers of excess cells.

Animals↗

PubMed2001

Postnatal development of the retinal projection to the nucleus of the optic tract and accessory optic nuclei in the hooded rat.

Retinal projections to the nucleus of the optic tract (NOT) and accessory optic nuclei (AON) were studied in the postnatal hooded rat after monocular injection of cholera toxin B subunit (CTB) into the vitreous chamber of the eye. At all postnatal ages, retinal axons were labeled sensitively; they revealed dense projections to the contralateral, and sparse but distinct projections to the ipsilateral, NOT and AON. The CTB labeling enabled the first delineation of the complete morphology of developing retinal axons in the ipsilateral NOT and AON. From postnatal day (P) 1 to P3, axons with complex growth cones were seen, and unbranched collaterals with simple growth cones increased and extended gradually. At P6, complex growth cones disappeared while branched collaterals with simple growth cones as well as small-sized varicosities increased. By P12 (two days before eye-opening) the adult-like pattern of terminal arbors appeared. The branched collaterals with tiny, small-sized varicosities present probably represented developing synaptic boutons. At P16 (after eye opening), the pattern of terminal arbors was well developed, almost to the same extent as in the adult. By contrast, a broadly distributed, transient retinal projection around NOT and AON was gradually eliminated; it started to disappear during the first few postnatal days, and was fully retracted by the time of eye-opening time to a pattern normal for the adult.

Animals↗

PubMed2003

Gene regulation of melatonin and dopamine receptors during eye development.

To gain insight into the role of melatonin and dopamine in retinal development, gene expression of two melatonin receptors, MT1 and MT2, as well as five dopamine receptors, D1, D2, D3, D4 and D5, in the rat eye was analyzed by reverse transcription-polymerase chain reaction across various developmental stages. MT1 transcript levels reached maximum levels at embryonic day (E) 16 and then decreased gradually until reaching adult levels by postnatal day (P) 14. MT2 transcript levels similarly peaked at E16, but then decreased dramatically until birth to its lowest levels, which were maintained throughout the postnatal period. Thus, gene expression of both the MT1 and MT2 receptors showed a striking inverse correlation with maturation of the eye. In contrast to melatonin receptors, gene expression of all dopamine receptor subtypes, except for D3, showed only an increase as development proceeds with highest levels in adulthood. The D3 message was not detected throughout the developmental period examined. Gene expression of D1-like receptors, D1 and D5, showed a substantial increase to adult levels during the fetal period at E16 and E20, respectively. Transcript levels of D2-like receptors, D2 and D4, on the other hand, were not detected before birth but increased significantly to adult levels by P7 and P14, respectively. The present findings suggest the presence of unique developmental mechanisms by which transcription of various G protein-coupled receptors are regulated in the eye.

Aging↗

PubMed1992

Quantitative assessment of growth stimulating activity of the vitreous during PVR.

This report postulates that the activity of cellular proliferation along the surface of the retina during proliferative vitreoretinopathy (PVR) is reflected in the aggregate effect of proliferation-inducing growth factors in the vitreous. A method for quantifying the "net" proliferation-inducing capacity of an individual vitreous sample was developed and this assay was used to evaluate the vitreous proliferative activity in a model for experimental PVR. Vitreous was aspirated sequentially after onset of fibroblast-induced PVR in a rabbit model. A simple bioassay for the "aggregate" stimulating activity was developed and each sample was assigned a quantitative value in terms of "proliferation units" (PU). Experimental eyes demonstrated a wide range of stimulating activity (0-1765 PU), but control eyes showed uniformly low levels of activity (0-337 PU). Experimental eyes that ultimately developed retinal detachment displayed higher levels of proliferative activity than did those eyes destined to remain attached. The differences were statistically different by day 3, prior to the onset of clinical retinal changes. We conclude that quantification of vitreous proliferation-stimulating activity is possible and that this method might be useful for screening eyes at high risk for the development of recurrent retinal detachment from PVR.

Animals↗