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PubMed1983

Prevention of experimental massive peri-retinal proliferation by 5-fluoro-uracil.

An intermediate report, on the effect of 1 mg 5-Fluoro-uracil on prevention of intra-vitreal fibroblast proliferation, strand formation and traction retinal detachment development in rabbits, is presented. The drug, which appeared to be nontoxic to the ocular tissues, prevented significantly the development of vitreous strands and traction retinal detachment in 10 out of 19 eyes (detachment rate, 47.3%), in comparison to 18 (control) eyes, out of 19, that did develop intravitreal strand and traction retinal detachment (94.7%).

Animals↗
PubMed1990

An ultrastructural and morphometric study of the effect of removal of retinal input on the development of the dorsal lateral geniculate nucleus.

In normal development, cell layers in the dorsal lateral geniculate nucleus (dLGN) segregate from a relatively homogeneous cell group. If all retinal input is removed prior to this segregation, the layers fail to form. In the present study, we used ultrastructural and morphometric analyses to study dLGN development in the tree shrew following neonatal removal of retinal input. The goal of the present study was to determine whether there are differences between normal animals and enucleates in the development of dLGN cells and their interrelationships with each other and/or with the surrounding glia, which might explain the failure of cellular lamination in enucleated animals. The results indicate that although the development in enucleated animals may take place somewhat more slowly, by P90 cell size and density are not significantly different from normal. These results, coupled with the observation that the dLGN in enucleates is smaller than in normals, suggest that the removal of retinal input results in dLGN cell loss. At both the light and electron microscopic level, cells in the developing normal dLGN are arranged in bands of immediately adjacent cells. In enucleates, dLGN cells are less frequently in immediate contact and are arranged in small groups or clumps which may be separated by degenerating cells. The present data suggest that the presence of retinal input may be necessary to allow dLGN cells to maintain the intercellular relationships necessary for laminar segregation to take place.

Animals↗
PubMed2004

Expression of Hsp27 in retinal ganglion cells of the rat during postnatal development.

The small heat shock protein Hsp27 has been shown to protect neurons from apoptosis. We have recently shown the expression of Hsp27 in a subset of injured adult retinal ganglion cells (RGCs), a response that is muted by the administration of brain-derived neurotrophic factor. This work has suggested a role for Hsp27 in the long-term survival of RGCs following injury. The purpose of this study was to investigate the expression of Hsp27 during postnatal retinal development, based on Hsp27's role as a neuronal survival factor and on its up-regulation in the adult injured retina. Expression of Hsp27 in the developing retina was examined at various times postnatally (between P0 and P24) by using immunohistochemical techniques. We report that Hsp27 expression peaks in the ganglion cell layer between P6 and P12 and is not detected at earlier (P0-P3) or later (P15-P24) times. Double labeling of the Hsp27-positive cells with Fluorogold applied to the superior colliculus confirmed that Hsp27-positive cells in the ganglion cell layer are RGCs. We have shown developmentally regulated expression of Hsp27 in RGCs of the postnatal rat. The retinal expression of Hsp27 correlates temporally with innervation of the tectum by late-born RGCs and with onset of spontaneous retinotectal activity. We propose that the expression of Hsp27 may play an important role in retinal development during a critical period of RGC functional connectivity with the superior colliculus.

Animals↗
PubMed2002

Putting neurons in the right places: local interactions in the genesis of retinal architecture.

Development of the nervous system can be schematically summarized as (1) making the necessary cells, (2) putting these cells in the right places, and then (3) connecting them appropriately. Each of these steps represents an enormous challenge to our understanding. Focusing on the vertebrate retina, I will consider the question of what defines the right place for a neuron to go. I will illustrate data pointing to the prominent role played by short-range cellular interactions, possibly coordinated by global factors, and will discuss how a few sets of local rules could control cell positioning and proper wiring in retinal circuits.

Animals↗
PubMed2001

The zebrafish as a model visual system.

The zebrafish has become an important vertebrate model in developmental neuroscience because it is a useful model for embryology, developmental biology, and genetic analysis. The similarities of its visual system to that of other vertebrates also make this animal a valuable model in vision science. The anatomical, physiological, and behavioral components of zebrafish visual processing have been studied in adult and in developing zebrafish. Its retinal anatomy continues to develop following hatching, providing an opportunity to correlate the development of retinal structure with visual physiology and behavior. In addition, a number of genetic mutations have been developed which are used to examine the contributions of genetics to visual development and function. This article will provide an overview of studies of zebrafish anatomical, physiological and behavioral processing, and the effects if genetic and environmental manipulations on visual development.

Aging↗
PubMed1982

Bilateral acute retinal necrosis. Clinical and ultrastructural study.

In a 28-year-old man with bilateral acute retinal necrosis, a severe, bilateral panuveitis, necrotizing retinitis, and retinal vasculitis developed. Severe vitreous traction on atrophic retina resulted in bilateral giant retinal tears with an inoperable retinal detachment in the right eye. A retinal detachment developed in the left eye that was reattached after a pars plana vitrectomy and two scleral buckling procedures, but ultimately became inoperable. Large numbers of lymphocytes in the vitreous aspirate and depressed serum complement levels may indicate that an immune mechanism was involved in the necrotizing retinitis. We present the first electron microscopic evidence, to our knowledge, that preretinal membranes occurring in rhegmatogenous retinal detachment due to bilateral acute retinal necrosis arise from retinal pigment epithelium.

Acute Disease↗
PubMed1984

The retinal lesions of the acquired immune deficiency syndrome.

AIDS is a reliably diagnosed disease that is indicative of an underlying cellular immunodeficiency with no other cause for the disorder. To date over 2000 cases have been reported in North America and Europe and the number is rising. Patients fulfilling the definition for AIDS have included male homosexuals, IV drug abusers of both sexes, people from Haiti, heterosexual partners of AIDS patients, hemophiliacs, and some patients who fit no particular pattern. The etiology has been attributed to factors acting singly or in synergy namely that repeated exposure to CMV, semen, or other antigens results in progressive cellular immunodeficiency, or alternatively, a novel virus has an etiologic role. The epidemiology of the syndrome suggests a horizontally transmissible agent. The spectrum of opportunistic infections observed in AIDS patients is well documented. A higher incidence of KS as well as squamous carcinoma of the oral cavity, cloacogenic carcinoma of the rectum, primary lymphomas of the brain, and systemic Burkitt's-like lymphoma has been noted. Seventy-one patients with AIDS were examined and followed during the course of their disease. Forty-one patients had definite retinal lesions at the time of examination. The most common intraretinal finding was CMV retinitis which displayed the typical white, crumbly areas of retinal necrosis and hemorrhage. Optic nerve involvement was quite common. The development of retinitis was a harbinger of eventual death as it was a progressive and a nontreatable disorder, lasting about 6 months. The second most common retinal finding was cotton wool spots, the lesions were usually present during the course of PCP and were due to microvascular damage in the retina from circulating immune complexes. No organisms were demonstrated in the retina. One AIDS patient who had been an IV drug abuser developed fungal retinitis due to Candida albicans. The patient eventually died from Candida sepsis. One patient had acquired toxoplasmosis retinochoroiditis. Examination revealed a large active intraretinal focus of infection. No other retinal lesion was noted. The patient, a homosexual, died from a toxoplasmosis brain abscess. The patient with AIDS is in a continuing struggle for survival against a myriad assortment of opportunistic infectious agents. Careful initial ophthalmological examination and long-term follow-up are mandatory.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Regional uveal response to increased nutritional needs in the retinal zone of the developing eye demonstrated in an eye with retinoblastoma.

The outer layers of the normal retina depend on indirect nutrition originating in the choriocapillaris and supplied to the retina by way of the pigment epithelium. An eye with exophytic retinoblastoma is used to demonstrate increased vascularity and tissue substance in the adjacent choroid believed to be indirectly induced by a regional increase in nutritional requirements in the retinal zone of a developing eye.

Blood Circulation↗
PubMed1999

Quantitative cytomegalovirus DNA level in the blood and its relationship to cytomegalovirus retinitis in patients with acquired immune deficiency syndrome.

OBJECTIVE: A pilot study was performed to determine whether relationships exist between changes in a quantitative solution hybridization assay for cytomegalovirus (CMV) DNA in the blood and development of CMV retinitis, development of nonocular CMV disease, or reactivation of pre-existing CMV retinitis lesions. DESIGN: Observational case series. PARTICIPANTS: Two groups of human immunodeficiency virus-infected patients: 10 CMV antibody-positive patients with CD4+ T-lymphocyte counts of less than 50 ml and no CMV disease at baseline and 11 patients with CMV retinitis but no extraocular CMV disease at baseline. INTERVENTION: Quantitative changes in leukocyte-associated CMV DNA levels were observed over time. Anti-CMV therapies were based on clinical findings only. MAIN OUTCOME MEASURES: Development of CMV end-organ disease or change in activity of pre-existing CMV retinitis lesions was measured. RESULTS: Among patients with no CMV disease at baseline, four had CMV disease develop during follow-up (three cases of CMV retinitis, one case of presumed CMV esophagitis); all had CMV DNA levels greater than 5000 genomes/ml before the onset of CMV disease. The remaining six patients had levels less than 5000 genomes/ml throughout follow-up (P = 0.05). Among patients with CMV retinitis at baseline, all whose CMV DNA blood levels rose more than tenfold had extraocular CMV disease or reactivation of CMV retinitis develop. Raised CMV DNA blood levels were not seen in every patient with clinical reactivation of CMV retinitis. CONCLUSION: Elevated or rising CMV DNA blood levels appear to be associated with the development of CMV disease in individuals with low CD4+ T-lymphocyte counts. In patients with CMV retinitis, rising levels appear to be associated with the development of extraocular CMV disease or reactivation of CMV retinitis. Conversely, reactivation of CMV retinitis also may occur in the absence of changes in CMV DNA blood levels. Further studies are warranted to determine whether changes in CMV blood levels can be used as a guide for preemptive therapy to prevent reactivation of CMV retinitis lesions or to help choose between local and systemic therapy for management of reactivations.

AIDS-Related Opportunistic Infections↗
PubMed2000

Characterization of a chicken retinoid X receptor-gamma gene promoter and identification of sequences that direct expression in retinal cells.

Development of the cellular complexity of the vertebrate neural retina relies on an intricate interplay between extracellular signals and intracellular factors. In particular, transcription factors play a key role in determining the competence of cells to respond to extracellular signals. We have previously shown that, in the developing chick neural retina, expression of the retinoid X receptor-gamma (RXR-gamma2) nuclear receptor gene is restricted to photoreceptors. To characterize the mechanisms that regulate expression of this gene in the neural retina, we isolated a chicken RXR-gamma genomic clone containing the RXR-gamma2 promoter and mapped the transcription initiation site by means of ribonuclease protection. We analysed promoter activity by transient transfection of luciferase reporter gene constructs into cultured cells isolated from embryonic-chick neural retina or facial mesenchyme, which does not normally express detectable RXR-gamma2 transcripts. The DNA fragment lying between nucleotides -657 and +37 with respect to the transcription initiation site had basal promoter activity in both cell types. The fragment lying between nucleotides -1198 and -991 directed 10-20-fold higher levels of luciferase activity in neural retina cells, but only basal levels in facial mesenchyme cells. This 208 bp fragment also enhanced the activity of the simian-virus-40 promoter, when placed upstream in either orientation. Electrophoretic-mobility-shift assays using this 208 bp fragment demonstrated the formation of four neural retina-specific protein-DNA complexes. These results indicate that regulation of RXR-gamma2 transcription in the developing chick neural retina involves the binding of one or more neural retina-specific protein factors to an enhancer element located approx. 1 kbp upstream of the transcription initiation site.

Animals↗
PubMed1991

[A case of central retinal vein occlusion accompanied by central retinal artery occlusion].

A 81-year-old woman developed central retinal vein occlusion (CRVO) in her left eye subsequent to central retinal artery occlusion (CRAO). She noticed sudden visual loss in the left eye. At initial examination, her left visual acuity was 0.03, and only a small visual field was preserved at temporal area. The left fundus showed findings of mild non-ischemic CRVO. In addition white clouded retina was recognized at the left posterior pole which indicated CRAO. FAG showed remarkably prolonged arterial circulation, but no retinal capillary obliteration. Then retinal hemorrhage increased rapidly and her left eye developed hemorrhagic retinopathy. Two weeks after initial examination, FAG showed extensive retinal capillary obliteration. In this case it was supposed that central retinal artery occlusion due to arteriosclerosis produced ischemic capillaropathy and venous thrombosis, after which restoration of arterial circulation caused hemorrhagic retinopathy.

Aged↗
PubMed1994

Treatment of cytomegalovirus retinitis with an intraocular sustained-release ganciclovir implant. A randomized controlled clinical trial.

BACKGROUND AND METHODS: We performed a randomized controlled clinical trial to assess the safety and efficacy of a 1 microgram/h ganciclovir implant for the treatment of newly diagnosed cytomegalovirus (CMV) retinitis in patients with the acquired immunodeficiency syndrome (AIDS). Patients with previously untreated peripheral CMV retinitis were randomly assigned either to immediate treatment with the ganciclovir implant or to deferred treatment. Standardized fundus photographs were taken at 2-week intervals and analyzed in a masked fashion. The study end point was progression of retinitis based on the photographic assessment. RESULTS: Twenty-six patients (30 eyes) were enrolled. The median time to progression of retinitis was 15 days in the deferred treatment group (n = 16) vs 226 days in the immediate treatment group (n = 14) (P < .00001, log-rank test). During the study, 39 primary implants and 12 exchange implants were placed in immediate-treatment eyes, deferred-treatment eyes that progressed, or contralateral eyes that developed CMV retinitis. Postoperative complications in the total series included seven late retinal detachments and one retinal tear without detachment. Final visual acuity was 20/25 or better in 34 of 39 eyes. The estimated risk of developing CMV retinitis in the fellow eye was 50% at 6 months. Biopsy-proven visceral CMV disease developed in eight (31%) of 26 patients. The median survival was 295 days. CONCLUSION: The ganciclovir implant is effective for the treatment of CMV retinitis. Patients with unilateral CMV retinitis treated with the implant are likely to develop CMV retinitis in the fellow eye, and some patients will develop visceral CMV disease.

AIDS-Related Opportunistic Infections↗
PubMed1996

Development of an integrated automated retinal surgical laser system.

Researchers at the University of Texas and the USAF Academy have worked toward the development of a retinal robotic laser system. The overall goal of this ongoing project is to precisely place and control the depth of laser lesions for the treatment of various retinal diseases such as diabetic retinopathy and retinal tears. Separate low speed prototype subsystems have been developed to control lesion depth using lesion reflectance feedback parameters and lesion placement using retinal vessels as tracking landmarks. Both subsystems have been successfully demonstrated in vivo on pigmented rabbits using an argon continuous wave laser. Preliminary testing on rhesus primate subjects have been accomplished with the CW argon laser and also the ultrashort pulse laser. Recent efforts have concentrated on combining the two subsystems into a single prototype capable of simultaneously controlling both lesion depth and placement. We have designated this combined system CALOSOS for Computer Aided Laser Optics System for Ophthalmic Surgery. Several interesting areas of study have developed in integrating the two subsystems: 1) "doughnut" shaped lesions that occur under certain combinations of laser power, spot size, and irradiation time complicating measurements of central lesion reflectance, 2) the optimal retinal field of view (FOV) to achieve both tracking and lesion parameter control, and 3) development of a hybrid analog/digital tracker using confocal reflectometry to achieve retinal tracking speeds of up to 100 dgs. This presentation will discuss these design issues of this clinically significant prototype system. Details of the hybrid prototype system are provided in "Hybrid Eye Tracking for Computer-Aided Retinal Surgery" at this conference. The paper will close with remaining technical hurdles to clear prior to testing the full-up clinical prototype system.

Animals↗
PubMed2003

Retinal tear and detachment after transpupillary thermotherapy for choroidal melanoma.

PURPOSE: To report a side effect of transpupillary thermotherapy for choroidal melanoma. DESIGN: Small case series. METHODS: Review of clinical charts and photographs in a private retina practice. RESULTS: Retinal tears developed in two patients after transpupillary thermotherapy for choroidal melanoma. In one patient a secondary rhegmatogenous retinal detachment developed. CONCLUSIONS: Transpupillary thermotherapy can result in vitreous traction on the retina over the choroidal tumor, which can lead to a retinal tear and to retinal detachment. Patients should be warned about this possibility and advised to be examined should photopsias or new floaters develop after treatment.

Aged↗
PubMed1995

Progressive retinal toxicity in neonatal rats treated with D,L-2-amino-3-phosphonopropionate (D,L-AP3).

D,L-2-amino-3-phosphonopropionate (D,L-AP3) has complex pharmacologic activity at central nervous system metabotropic glutamate receptors important in excitatory neurotransmission and development. Previous studies have described retinal and optic nerve atrophy in adult rats after postnatal treatment with D,L-AP3. Using neonatal male Sprague-Dawley rats, the present studies examined normal postnatal retinal development (n = 20) and the progression of retinal toxicity induced by D,L-AP3 (n = 30). Retinal development was examined by light microscopy on postnatal days (PNDs) 5, 9, 12, 16, and 22. Between PNDs 5 and 16, the retina underwent considerable postnatal differentiation. A prominent neuroblastic layer evident on PND 5 differentiated into outer retinal layers by PND 16. To examine the effects of D,L-AP3, neonatal rats were treated intraperitoneally with sterile water or 400 mg/kg/day D,L-AP3 on PNDs 3-6. On PNDs 5, 7, 10, 15, and 20, retinas were examined by light and electron microscopy. On PNDs 5 and 7, cells with swollen, pale cytoplasm were evident in the more differentiated inner nuclear layer and in the middle of the developing neuroblastic layer. Retinal toxicity rapidly progressed after treatment, because developing outer retinal layers had cytoplasmic swelling, nuclear pyknosis, and necrosis on PND 10. By PNDs 15 and 20, retinal dystrophy was severe and involved primarily outer layers. This study showed that early postnatal treatment with D,L-AP3 initiates rapidly progressing retinal toxicity, thus implicating metabotropic glutamate receptors in the postnatal retinal development of rats.

Alanine↗
PubMed1982

Assessing the risk of retinitis pigmentosa with age-of-onset data.

Early characteristic electrophysiologic and ophthalmoscopic changes may help predict the development of retinitis pigmentosa. Until recently, if these were absent or equivocal, the ophthalmologist had to rely on the family pattern of transmission and simple Mendelian genetic methods to calculate the patient's risk of manifesting the disease. We used data on age of onset of subjective night blindness in 229 patients with retinitis pigmentosa (189 with autosomal recessive disease, 27 with autosomal dominant disease, and 13 with X-chromosome-linked disease) with Bayesian methods of probability calculation to predict the risk of retinitis pigmentosa development in a given patient more accurately than is possible with simple Mendelian methods. The risk for one subject used as an example was reduced from 50% to 12.9%.

Adolescent↗