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PubMed2005

Characterization of a transgenic mouse line lacking photoreceptor development within the ventral retina.

A unique transgenic mouse line was generated by incorporating a minigene that contained a cone-specific human cone transducin alpha-subunit (GNAT2) promoter, an attenuated diphtheria toxin A (DTA) gene, and an enhancer element from human interphotoreceptor retinoid-binding protein (IRBP) gene. This transgenic mouse line is designated h-GNAT2pro-DTA. During postnatal retinal development, both transgenic and non-transgenic retinas showed similar morphology and thickness at P1. Between ages P8 and P30, all retinal layers became recognizable in non-transgenic and also in transgenic dorsal retinas. However, in the ventral retina of the transgenic mice the photoreceptor layers did not develop. This aberration occurred as a result of abnormal cellular development, rather than as a consequence of retinal degeneration. In adult transgenic animals, approximately 44% of the retina located dorsally appeared morphologically normal, whereas 32% of the retina located ventrally was completely lacking photoreceptor development. The 24% mid-retinal region exhibited transitional morphology containing malformed photoreceptors. At P360 or older, the thickness of retina layers was reduced in both dorsal and ventral regions. The abnormality observed in transgenic retinas involved mainly the photoreceptors; the other retinal cell types were all present in both dorsal and ventral retinas. Since the DTA gene was only expressed in cone cells, the absence of cone photoreceptors in the transgenic retina was to be expected. However, what was unexpected was the concomitant absence of rod photoreceptors in the ventral retina, suggesting that the presence of cones may be important for the development of rods. This new transgenic line can lead to better understanding of photoreceptor development, and may serve as a new animal model for studying photoreceptor-related retinal diseases.

Animals↗
PubMed2003

[Retinal shortening: the most severe form of proliferative vitreoretinopathy (PVR)].

PURPOSE: To identify the clinical characteristics of patients developing retinal shortening due to intraretinal PVR. METHODS: Observational and retrospective cohort study on 110 PVR patients operated on between 2000 and 2001. During surgery, after removing epiretinal membranes and ruling out the presence of subretinal membranes, a perfluorocarbon liquid was injected. Those cases in which retinal flattening was not accomplished, were considered intraretinal PVR (group 1). Those in which retinal flattening allowed endolaser application, were taken as the control group (group 2). Clinical features of both groups were compared by chi-square test. RESULTS: 60 cases (54.5%, CI 95%: 40.5-68.5) showed retinal shortening (group 1). In 24 cases (21.8%, CI 95%: 12.9-30.7) complete retinal flattening was accomplished (group 2). In 26 cases (23.6%), evaluation was inconclusive. In 9 out of the 60 cases of group 1 (15%) a retinectomy was necessary to reattach the retina. Differences between both groups were not statistically significant for any of the clinical variables. However, the number of retinal detachments of more than 60 days of evolution was significantly higher in retinectomized eyes (20.7%) than in group 1 (3.7%) (p=0.04). CONCLUSIONS: Retinal shortening is a relatively frequent phenomenon in PVR. Further studies are necessary to characterize this clinical presentation of PVR and its pathogenesis.

Case-Control Studies↗
PubMed1988

Herpes simplex virus type 1 induces anterior chamber-associated immune deviation (ACAID) in mouse strains resistant to intraocular infection.

Inoculation of herpes simplex virus Type 1 into the anterior chamber of BALB/c mice induces a characteristic ocular infection involving primarily the anterior segment of virus-injected eyes and the retina of contralateral uninjected eyes. In the BALB/c strain, which is susceptible to herpetic retinitis, anti-HSV delayed hypersensitivity responses are actively suppressed, although anti-HSV antibody responses remain intact. We previously demonstrated that C57B1/6 mice, as well as (BALB/c X C57B1/6) F1 are highly resistant to HSV-1 retinitis. Studies have now been performed to determine the relationship between systemic immune responses to HSV and the resistance of C57B1/6 and the (BALB/c X C57B1/6) F1 to develop retinitis after inoculation of HSV into one anterior chamber. Despite the resistance to herpetic retinitis by B6 and F1 mice, both strains developed a pattern of systemic immune responses to HSV similar to those observed in the susceptible BALB/c mice. Therefore, resistance to retinal infection with HSV-1 does not appear to correlate with the pattern of systemic cell-mediated or humoral immune responses to intracameral HSV-1.

Animals↗
PubMed1986

Ommatidial development in Drosophila eye disc fragments.

We have tested the hypothesis that the leading edge of the growing Drosophila compound eye acts as a template that organizes unpatterned cells of the retinal epithelium into the accurate cellular mosaic of the eye. Unpatterned fragments of the epithelium, not containing the leading edge of the growing field, were transplanted into larval hosts. After hosts pupated, the implants were recovered; most contained ommatidia, demonstrating that the leading edge of the growing eye pattern is not required for its propagation. In a second set of experiments, implants were recovered before hosts pupated and examined for ommatidia using a monoclonal antibody. These implants likewise differentiated ommatidia and the temporal progress of retinal development in the implants mirrored that of normal development. A schedule of ommatidial development thus appears to be mapped onto the retinal epithelium in advance of the leading edge.

Animals↗
PubMed2005

Lens opacity and photoreceptor degeneration in the zebrafish lens opaque mutant.

The zebrafish lens opaque (lop) mutant was identified in a chemical mutagenesis screen. The lop mutant, which develops normally through 4 days postfertilization (dpf), exhibits several signs of lens and retinal degeneration at 7 dpf. Histology revealed disrupted lens fibers and increased numbers of nucleated cells within the mutant lens and anterior chamber. The mutant lens also exhibited aberrant epithelial cell morphologies and lacked a definitive transition zone, which suggests that secondary fiber differentiation was interrupted. In addition, the mutant exhibits severely reduced photoreceptors and a reduction in the number of horizontal cells at 7 dpf. Other retinal cell classes appeared unaffected in the mutant. Transmission electron microscopy and opsin immunohistochemistry showed that the different photoreceptor types were generated at the retinal margin, but the rods and cones failed to mature and disappeared. The mutant lens and retina also displayed increased cell proliferation based on proliferating cell nuclear antigen immunolabeling, suggesting that the lens opacity was due to unregulated cell proliferation and undifferentiated cell accumulation within the mutant lens. The lop mutant phenotype supports recent studies showing the lens has a role in regulating teleost retinal development.

Animals↗
PubMed2004

Valgancyclovir as maintenance therapy for cytomegalovirus retinitis in a lung transplant patient--a case report.

UNLABELLED: The purpose of this article is to report the use of valgancyclovir as maintenance therapy for cytomegalovirus (CMV) retinitis in a lung transplanted patient. RESULT: A 30-year-old woman with underlying pulmonary lymphangioleiomyomatosis received a lung transplant 1 year ago. CMV retinitis developed 4 months later but subsided after intravenous ganciclovir treatment. Unfortunately, the CMV retinitis recurred three times in 1 year while on oral ganciclovir maintenance therapy. To treat the latest relapse, valgancyclovir 900 mg once daily was used as maintenance therapy after intravenous gancyclovir induction. With a 6-month follow-up, the fundoscopic examination revealed old atrophic scar and no active CMV retinits. The patient was able to maintain best-corrected visual acuity of 20/20 in both eyes. In conclusion, Valganciclovir may be used as maintenance therapy in CMV retinitis.

Adult↗
PubMed2004

Severe retinal degeneration associated with disruption of semaphorin 4A.

PURPOSE: Semaphorin 4A (Sema4A) is a member of the transmembrane class 4 family of semaphorins. It has recently been shown to participate in cell-cell communication in the immune system. High levels of sema4A are also present in brain and eye, but its function in the central nervous system has not been studied. To investigate the function of Sema4A, we generated mice deficient in this transmembrane signaling molecule. METHODS: An embryonic stem (ES) cell clone with a retroviral gene-trap insertion in the sema4A gene was used to generate mice lacking this transmembrane semaphorin. Fundus photography, fluorescein angiography, and electroretinography were used to evaluate retinal anatomy and physiology in mice lacking Sema4A. Electron microscopy and immunohistochemistry with cell-type-specific markers were used to characterize retinal development. In situ hybridization with sema4A-specific riboprobes was used to localize expression of this gene in the developing and adult eye. RESULTS: Fundus photography performed at 14 weeks of age revealed severe retinal degeneration, attenuated retinal vessels, and depigmentation in mice lacking Sema4A. At this age, the outer nuclear layer was reduced to a single row of photoreceptor cells, and the outer plexiform layer was thin and disorganized. Disruption of Sema4A also compromised the physiological function of both rod and cone photoreceptors. Developmental studies in Sema4A-deficient mice revealed abnormal morphology of photoreceptor outer segments during the time at which they establish contacts with apical microvilli of the retinal pigment epithelium (RPE). Sema4A is expressed in the inner retina and RPE during the time at which photoreceptor outer segments elongate. CONCLUSIONS: These findings identify a previously unknown function of Sema4A in the developing visual system and provide a useful model for understanding cell-cell interactions that occur between photoreceptors and the RPE.

Animals↗
PubMedDate not supplied

Management and results of retinal detachment after silicone oil removal.

Of the 168 eyes undergoing silicone oil removal from 1993 to 2000, 34 developed retinal detachment after the removal of silicone oil. The management and the results of the 34 eyes were reviewed. Surgical procedures included pars plana vitrectomy, encircling band, cryocoagulation, endotamponade. Five of the 34 eyes had a second retinal detachment after these operations. One of these 5 eyes had a third retinal detachment. Final retinal reattachment was achieved in all eyes. Visual acuity decreased in 16 of the 34 eyes with retinal detachment, and 18 of the 34 eyes had a visual acuity of less than 0.02. These results show that surgery for retinal detachment after silicone oil removal yields a high rate of anatomic success, while the visual outcome is poor for a substantial number of patients.

Adult↗
PubMed1989

Herpes simplex retinitis in the mouse. Clinicopathologic correlations.

BALB/c mice inoculated with herpes simplex virus type 1 in one anterior chamber develop retinitis with subsequent retinal necrosis in the contralateral eye. The clinical features of this disease were characterized with indirect ophthalmoscopy and fundus photography. Three phases of the disease were delineated: (1) acute retinitis; (2) retinal necrosis; and (3) resolution; the clinical findings in each phase were correlated with the microscopic features. In addition, we compared the virus titers from individual animals with and without clinical evidence of retinitis to demonstrate that retinal inflammation correlated with the titer of virus in the uninoculated eye. This animal model is useful for the analysis of the clinical, virologic and immunologic manifestations of herpetic retinitis.

Animals↗
PubMed1999

Differential expression of hepatocyte growth factor and its receptor, c-Met in the rat retina during development.

Hepatocyte growth factor (HGF) is a pleiotrophic factor with mitogenic, motogenic, and morphogenic activities. Recent evidence has suggested that HGF plays an important role in the development and maintenance of the nervous system. In this study, we examined spatial and temporal expression of HGF and its receptor, c-Met, during retinal development at RNA or protein levels. Competitive RT-PCR revealed that HGF and c-met mRNA expressions were up-regulated during the development and sustained at high levels in adulthood. By immunohistochemical analysis, we demonstrated that c-Met-immunoreactivity (IR) was present in the major classes of retinal neurons after their differentiation. In the adult, c-Met-IR was predominantly present in the photoreceptors. In contrast, HGF-IR was observed from P7 and thereafter in ganglion cells and the inner nuclear layer, but not in other layers. Differential or co-localization of HGF and c-Met indicates the autocrine or paracrine action of HGF depending on the cell types and developmental stages. Moreover, dynamic regulation of HGF and c-Met implicates their multiple roles in the development, maintenance and modification of retinal system.

Animals↗
PubMedDate not supplied

Effects of prenatal cocaine exposure in the retinal ganglion cell layer of the rat. A morphometric analysis.

To study the effects of prenatal cocaine-exposure on the developing retinal ganglion cell layer of the rat, female Wistar rats were administered subcutaneously (sc) cocaine hydrochloride (60 mg/kg body wt/d) or saline, or were not manipulated from gestational d 8-22. Male offspring were sacrificed at postnatal day 14 and 30. Radial semithin sections of epon-embedded flat mounts of the retinal quadrants were used to evaluate the following parameters along the centroperipheral axis: 1. Thickness of ganglion cells plus nerve fiber layer; 2. Nuclear size of ganglion cell layer neurons; and 3. Linear density (number per unit length) of ganglion cell layer neurons. To study the effects of cocaine and age on the retinal areas (temporal/nasal, dorsal/ventral), a repeated measures analysis of variance was used for each of the parameters mentioned above. All parameters were affected by prenatal exposure to cocaine. The thickness of the ganglion cell plus nerve fiber layer was reduced in cocaine-exposed rats in comparison with the saline group. Nuclear diameters were smaller in the cocaine than in the saline and control groups. The linear density was higher in the cocaine-exposed group than in the control and saline groups. The age-dependent decrease in the linear density from postnatal day 14-30 was higher in the cocaine-exposed rats than in the saline group; the decrease in the linear density along the centroperipheral axis found in both the control and saline groups was not significant in the cocaine-treated group. These morphometric findings strongly support the view that prenatal cocaine-exposure induces marked changes in the organization of the developing retina.

Aging↗
PubMed2005

Optic chiasm formation in humans is independent of foveal development.

A failure of human foveal development only occurs in two genetically determined conditions; aniridia (Pax6 mutation) and albinism (tyrosinase mutation). The chiasmatic pathways from this region are disrupted in albinism and central retinal blood vessel patterns are abnormal. It is assumed that these three abnormalities have a common mechanism. Here we investigate whether similar abnormalities are present in subjects with aniridia. Using fundus photographs it is shown that abnormal blood vessel patterns are present in aniridia, but these significantly differ from those in albinos. Using electrophysiological techniques, abnormal hemispheric projections through the chiasm are demonstrated in albinos, but aniridics do not differ from normal subjects. These results demonstrate that although mutations in Pax6 and tyrosinase both affect central retinal development, they have a fundamentally different impact on the formation of the retinal vasculature and the projections from this region. This strongly suggests that separate mechanisms regulate the development of the central retina and decussation patterns at the optic chiasm.

Adult↗
PubMedDate not supplied

Myopia predicts better outcome in persistent hyperplastic primary vitreous.

PURPOSE: Persistent hyperplastic primary vitreous (PHPV) is a congenital disorder that presents with a spectrum of ocular anomalies, including cataracts, microphthalmia, and hyaloid vessel remnants. Severe visual loss due to secondary glaucoma and retinal detachment is common. This report evaluates the visual outcome of a variant of PHPV with myopia not associated with glaucoma. METHODS: The records of 23 consecutive patients with the diagnosis of PHPV (all unilateral) from October 1992 to August 1995 were reviewed. All but three patients had a cataract extraction procedure and all underwent amblyopia therapy. Eyes with a phakic myopic refractive error (Rx) or aphakic refractive correction < or = 8.5 diopters (D) in the immediate postoperative period were designated as myopic. RESULTS: Six patients were in the myopic group (Group 1) and 17 in were the nonmyopic group (Group 2). The mean age of diagnosis was 21.1 months in Group 1 versus 2.0 months in Group 2, with a comparable follow-up period of 36 months. The mean preoperative Rx of Group 1 was -7.78 D. The mean aphakic Rx of Group 2 was +18.29 D. Average axial length measurement determined by echography was 22.46 mm in Group 1 and 14.03 mm in Group 2. The mean corneal diameter was 11.3 mm in Group 1 vs 8.9 mm in Group 2. In Group 2, seven eyes developed retinal detachment and four developed glaucoma. These complications did not develop in Group 1 during the follow-up period. Overall functional visual acuity was better in Group 1, with a median visual acuity at final follow up of 20/160, as compared with light perception for Group 2. CONCLUSIONS: PHPV eyes with myopia were not detected as early as the typical PHPV eyes, primarily because of less media opacification and near-normal corneal diameters. These eyes showed a more favorable visual outcome as they were less likely to develop typical PHPV-related postoperative complications. Myopic PHPV eyes may require a different management approach.

Child, Preschool↗
PubMed2000

Specific expression of the LIM/homeodomain protein Lim-1 in horizontal cells during retinogenesis.

The LIM/homeodomain transcription factor Lim-1 has been shown to play an essential role in early embryonic patterning during vertebrate development. Here we report the spatial and temporal expression patterns of Lim-1 during retinal development as detected by immunohistochemistry using a specific anti-Lim-1 antibody. By double-immunostaining, we have demonstrated for the first time that Lim-1 is exclusively expressed within the horizontal cell type in the adult retina. In the developing mouse retina, Lim-1 commences its expression in migratory horizontal cell precursors streaming toward the future horizontal cell layer in the ventricular zone. Moreover, its expression during retinogenesis is spatially and temporally coincident with that of the calcium-binding protein calbindin D-28k in horizontal cells. These data together suggest a possible role for Lim-1 in terminal differentiation and maintenance of horizontal cells, and that Lim-1 can serve as a specific molecular marker for the study of horizontal cell specification.

Animals↗
PubMed1992

Differential diagnosis of retinitis and choroiditis in patients with acquired immunodeficiency syndrome.

Patients with acquired immunodeficiency syndrome (AIDS) are at high risk for developing retinitis. The most common forms of retinitis in such patients are those caused by cytomegalovirus (CMV) and Toxoplasma; however, retinitis or choroiditis can also be caused by other viral, protozoal, bacterial, and fungal agents. Differential diagnosis of these infections is based on a number of factors, including ophthalmoscopic appearance, underlying disease, clinical history, and severity of underlying immunosuppression. Rapid and accurate diagnosis is essential in preserving functional vision, as some forms of retinitis are rapidly progressive and since appropriate treatment varies by diagnosis.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Thin slices of teleost retina continue to grow in culture.

Thin slices of differentiated fish retinas were maintained up to 5 days in culture conditions where they exhibited properties essentially identical to those found in retinas of intact animals. Retinal slices were prepared by embedding eyecups from young fish in agarose and sectioning them on a vibratome. Phenotypic integrity of specific cell types was maintained, as demonstrated by specific antibody staining patterns. Stem cells in the retinal margin and presumptive rod progenitor cells in the outer nuclear layer continued to proliferate in vitro, just as they do in vivo. Some of these cells differentiated in vitro as demonstrated by labelling both cell division and cell phenotype. After several days in culture, some regeneration-like responses were observed, such as growth of neurites and swelling of cell bodies in the ganglion cell layer. This retinal slice preparation appears to offer a unique opportunity for studying the interactions among developing retinal cells.

Animals↗
PubMed1982

Culture-proven cytomegalovirus retinitis in a homosexual man with the acquired immunodeficiency syndrome.

A 35-year-old homosexual man with cytomegalovirus viremia developed retinitis. He also had a new syndrome consisting of a persistent T-lymphocyte deficit, pneumocystis pneumonia, recurrent Candida albicans esophagitis, skin ulcerations caused by herpes simplex virus, Type 2, disseminated Mycobacterium avium-intracellulare infection, and molluscum contagiosum. Histopathologic examination revealed bilateral necrotizing retinitis with virions in retinal, choroidal, and optic nerve tissues. Postmortem cultures of retina and vitreous were positive for cytomegalovirus.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Muscarinic acetylcholine receptors in the normal, developing and regenerating newt retinas.

Immunoreactivity for m2 and m4 muscarinic acetylcholine receptors (mAChRs) was demonstrated in the adult newt retina. The m2 mAChR was localized to somata on either side of the inner plexiform layer (IPL), especially ganglion cells, and also distributed into two bands within the IPL. The distal band at a depth of 0-15% IPL co-localized with one of two choline acetyltransferase (ChAT) immunoreactive bands, while the proximal band at 85-100% depth did not overlap with either of the ChAT-ir bands. The m4 mAChR was localized to somata closely apposed to either side of the IPL, probably amacrine cell somata, and no immunoreactivity was detectable throughout the IPL. The time course of appearance of the m2 and m4 mAChRs was examined in both developing and regenerating retinas. Like acetylcholinesterase (AChE), the m2 was first detected in somata located at the most proximal level of the retina well before ChAT-ir cholinergic neurons appeared, while the m4 was detected at the time of appearance of ChAT, in both developing and regenerating retinas. When the outer plexiform layer (OPL) began to form, somata in the horizontal cell layer became transiently immunoreactive to the m2. The discrepancy in distribution of the m2 and ChAT in the IPL suggests that mAChR may play a role other than cholinergic neurotransmission. Furthermore, the similarity in time course of appearance of the m2 and m4, as well as other cholinergic system components [4], in both developing and regenerating retinas would suggest that the mechanisms that control neuronal differentiation during retinal development and regeneration are similar.

Acetylcholinesterase↗