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Biomedical subjects

Dennis M Marcus

Publications and source records attributed to Dennis M Marcus.

14 recordsLinked to original sources
PubMed2006

Ophthalmoscopic findings in malignant hypertension.

Malignant hypertension may present with retinopathy, choroidopathy, and optic neuropathy. Flame-shaped retinal hemorrhages, an early finding, are due to smooth muscle necrosis and bleeding along the nerve fiber layer. Cotton-wool spots, or cytoid bodies, are not exudates, but rather are retinal infarcts. Hypertensive optic neuropathy is a late finding. Optical coherence tomography is a relatively new imaging technique for evaluating retinal thickness and the location of pathology in patients with malignant hypertension.

Adult↗
PubMed2004

Alternative splicing of the APC gene in the neural retina and retinal pigment epithelium.

PURPOSE: Hypertrophy and hyperplasia of the retinal pigment epithelium (RPE) is associated with an inherited predisposition to human familial adenomatous polyposis coli, suggesting that expression of the adenomatous polyposis coli (APC) tumor suppressor may regulate RPE proliferation/differentiation. Distinctive APC isoforms exist in different cell types due to alternative splicing of the APC transcripts. We hypothesize that differences in expression patterns of APC protein isoforms are critical to RPE proliferation/differentiation. METHODS: To investigate these relationships, APC gene expression was characterized in the retinas and RPE from fetal and adult human and mouse, and in the epiretinal membranes (ERM) from 5 patients with proliferative vitreoretinopathy (PVR). Expression patterns of alternative splice-forms of APC transcripts were evaluated by comparative quantitative RT-PCR. Exon 1 of APC encodes a heptad repeat that confers the ability of APC to homodimerize. APC protein isoforms containing or lacking this heptad were characterized by western blot analysis and immunohistochemistry. RESULTS: Comparative quantitative RT-PCR demonstrated a predominant exon 1 containing, conventional APC splice-form in the early developing fetal RPE and retina, and in all the tested ERM samples from patients with PVR. This method also demonstrated an increased level of exon 1 lacking APC splice-form in the mature RPE and retina. Western blot analysis and immunofluorescence microscopy demonstrated the conventional APC only in the RPE, and the APC isoform without the first heptad repeat in both the retina and RPE. Immunofluorescence microscopy also demonstrated only the conventional APC in the ERM samples tested. CONCLUSIONS: These results suggest that alternative splicing of APC leads to differential APC expression with potentially unique functions. APC isoform without the first heptad repeat may play a role in cell cycle cessation in the adult retina and RPE, and the down regulation of this APC isoform may contribute to the potential of RPE to migrate and proliferate.

Adenomatous Polyposis Coli Protein↗
PubMed2004

The age-related macular degeneration radiotherapy trial (AMDRT): one year results from a pilot study.

PURPOSE: To assess the short-term safety and efficacy of treating subfoveal choroidal neovascularization (CNV) with external beam radiation delivered in 5 x 4 Gy fractions among patients having age-related macular degeneration (AMD). DESIGN: A multicenter prospective randomized controlled pilot study. METHODS: Eighty-eight patients were enrolled through 10 sites and were randomized to radiotherapy (20 Gy delivered in 5 daily fractions of 4 Gy each; 6 MV [N = 41]) or no radiotherapy (sham radiotherapy [N = 22] or observation [N = 25]). Eligibility criteria included visual acuity of at least 20/320 and subfoveal CNV not amenable to treatment. Randomization was stratified by lesion type (new or recurrent CNV) and blood (<50% or >/=50% of the lesion [N = 13]). The primary outcome measure was loss of >/=3 lines of visual acuity. Secondary outcome measures were angiographic response and side effects. RESULTS: At baseline, patient and ocular characteristics were similar between treatment groups. At six months, 9 radiated eyes (26%) and 17 eyes not radiated (49%) lost >/=3 lines of visual acuity (P = .04; stratified chi(2) test). At 12 months, 13 radiated eyes (42%) and 9 observed eyes (49%) lost >/=3 visual acuity lines (P = .60). The radiated group demonstrated smaller lesions and less fibrosis than the nonradiated group (P = .05 and .004, respectively) at 12 months. Radiation-induced complications were not observed except for one radiated eye with numerous cotton wool spots and possible radiation retinopathy. CONCLUSIONS: External beam radiation at 5 x 4 Gy may have a modest and short-lived (six month) benefit in preserving visual acuity.

Aged↗
PubMed2003

Surgical treatment of extensive peripapillary choroidal neovascularization in elderly patients.

PURPOSE: To report the visual outcomes and complications of surgical removal of extensive peripapillary choroidal neovascularization (PPCNV) in elderly patients. DESIGN: Retrospective review. PARTICIPANTS: Seventeen consecutive eyes of 17 patients older than age 55 undergoing PPCNV resection. METHODS: Retrospective review of eyes undergoing surgical removal of extensive PPCNV via pars plana vitrectomy. MAIN OUTCOME MEASURES: Preoperative and postoperative Snellen visual acuity. RESULTS: The mean age of patients was 76.9 years, and the mean duration of follow-up was 29.8 months. In 6 of 17 eyes, the PPCNV was extrafoveal; in two eyes, it was juxtafoveal; and in nine eyes, it was subfoveal. The cause of CNV was idiopathic (nine eyes), age-related macular degeneration (six eyes), presumed ocular histoplasmosis syndrome (one eye), and inflammation (one eye). All eyes were ineligible for laser treatment by MPS criteria. In eyes with extrafoveal CNV, the preoperative Snellen visual acuity ranged from 20/25 to 20/300, and the final visual acuity ranged from 20/40 to 20/800. The two eyes with juxtafoveal CNV had preoperative visual acuities of 20/125 and 20/300, and both had a postoperative acuity of 20/200. Eyes with subfoveal CNV had a range of preoperative visual acuity from 20/125 to 20/800, whereas the final visual acuity ranged from 20/30 to hand motions. Four of the nine eyes with subfoveal lesions had improved visual acuity. Overall, the final visual acuity was stable or improved in six eyes and worsened in 11 eyes. CNV recurrence was noted in four eyes and required reexcision, laser photocoagulation, or both. Surgical complications included retinal detachment (two eyes), retinal hole and epiretinal membrane (one eye), cystoid macular edema (two eyes), and subsequent cataract extraction (four eyes). CONCLUSIONS: Surgical removal of extensive PPCNV in the elderly does not often yield improvement or stabilization of visual acuity. However, 6 of 17 patients had stable or improved visual acuity.

Aged↗
PubMed2002

HGF regulation of RPE proliferation in an IL-1beta/retinal hole-induced rabbit model of PVR.

PURPOSE: To understand molecular events that lead to retinal pigment epithelial (RPE) cell proliferation and migration during the early phases of proliferative vitreoretinopathy (PVR) in a rabbit model. METHODS: Retinal holes were created and interleukin-1beta(IL-1beta) was injected intravitreally. Eyes were examined by indirect ophthalmoscopy and eyecup pieces containing retinal holes were analyzed at different times after the surgery up to 4 weeks. RPE proliferation and migration were examined by immunohistochemistry. Tyrosine phosphorylation of extracellular signal regulated kinase (ERK) and hepatocyte growth factor receptor (HGFR or c-met) was determined by immunoprecipitation and western blot analysis. Tyrosine phosphorylation of c-met and morphological studies was performed on vitreous treated ARPE-19 cells. Expression of c-jun was determined by Northern blot analysis. Matrix metalloproteinase (MMP) content in vitreous was assessed by zymography. RESULTS: Indirect ophthalmoscopy identified formation of epiretinal membrane and immunohistochemistry identified proliferative and migratory RPE and other cells in the posterior segment containing retinal holes at 4 weeks post-surgery. Tyrosine phosphorylation of ERK and c-met occurred in this segment within 30 min of surgery. ARPE-19 cells treated with vitreous from the 24 h post-surgical eyes, but not with control vitreous or IL-1beta, showed morphological changes and tyrosine phosphorylation of c-met. Northern blot analysis in this segment identified upregulation of c-jun within 30 min of surgery and the expression peaked at 72 h. Zymographic analysis of vitreous identified MMP-9 in 12-72 h post-surgery. CONCLUSIONS: These data suggest that the presence of retinal holes and IL-1beta may lead to activation of HGF, mitogen activated protein kinases (MAPK), c-jun and extracellular matrix remodeling, resulting in proliferative and migratory cells in the wounded retina.

Animals↗
PubMed2002

MAP kinase and beta-catenin signaling in HGF induced RPE migration.

PURPOSE: Hepatocyte growth factor (HGF) has been implicated in retinal pigment epithelial (RPE) cell proliferation and migration that occurs in proliferative retinal diseases such as proliferative vitreoretinopathy (PVR). The aim of this study is to investigate HGF induced signaling pathways that lead to RPE cell migration. METHODS: Localization of beta-catenin was determined by immunofluorescence. HGF induced migration of ARPE-19 cells was studied using a quantitative migration assay after wounding in the presence of a DNA polymerase inhibitor, and in the presence or absence of a mitogen activated protein kinase (MAP kinase) kinase inhibitor. C-jun expression was determined by semi-quantitative RT-PCR and by Northern blot analysis. P42/p44 MAP kinase activity was determined by western blot and by an immunoprecipitation kinase assay. Tyrosine phosphorylation of the HGF receptor (HGFR or c-met) and beta-catenin was determined by immunoprecipitation and western blot analysis. Transactivation activity of beta-catenin was determined by luciferase reporter gene analysis. RESULTS: Beta-catenin and E-cadherin were co-localized on the basal surface of the RPE in vivo. Diffusion of the cell surface-localized beta-catenin occurs in migratory cells in vitro in the presence of HGF. HGF induced a MAP kinase dependent ARPE-19 cell migration, which is accompanied with a transient increase of c-jun expression and concomitant increases of MAP kinase activity, tyrosine phosphorylation of HGFR and beta-catenin, increased cytosolic levels of beta-catenin, and transactivation activity of beta-catenin. Tyrosine phosphorylation of HGFR and beta-catenin occurs in the primary or passaged RPE cultures or proliferative ARPE-19 cells, but not freshly isolated RPE or differentiated ARPE-19 cells. CONCLUSIONS: This study defines the signal transduction pathways activated by HGF in RPE cells, leading to an increase in the MAP kinase activity and free pool of beta-catenin, and changes in gene expression. These findings are consistent with the hypothesis that both beta-catenin and MAP kinases are components of the HGF induced RPE migration that occurs in proliferative retinal diseases.

Aged↗
PubMed2002

Effects of sustained hyperoxia on revascularization in experimental retinopathy of prematurity.

PURPOSE: To investigate the effects of prolonged hyperoxia on vascular recovery and glia survival after experimentally induced retinopathy of prematurity (ROP) in the mouse. METHODS: The effects of hyperoxia on revascularization and vitreous neovascularization were compared between mice raised in 75% oxygen from postnatal day (P)7 to P12, followed by room air recovery and mice raised in 75% oxygen from P7 to P27. The status of astrocytes and Müller cells was evaluated by glial fibrillary acidic protein (GFAP) immunohistochemistry on retinal wholemounts and serial sections. A window of susceptibility to oxygen-induced vaso-obliteration was defined by comparing the extent of retinal vaso-obliteration resulting from 2 days of hyperoxia beginning on P7, P9, P11, P13, or P15. RESULTS: Oxygen-induced vaso-obliteration of retinal capillaries was limited to the period between birth and P15. Paradoxically, revascularization was markedly accelerated and neovascularization markedly reduced in mice maintained in prolonged hyperoxia (P7-P27) compared with mice recovering in room air. The extended use of 75% oxygen during the recovery period was associated with preservation of astrocytes and Müller cells in the avascular retina. CONCLUSIONS: The antiangiogenic effect of hyperoxia on retinal capillaries is strongly dependent on postnatal age. A protocol of continuous 75% supplemental oxygen accelerates recovery of inner retinal vasculature and prevents vitreous neovascularization, by a mechanism that may involve preservation of inner retinal glia.

Animals↗
PubMedDate not supplied

Retinal vascular integrity following correction of diabetic ketoacidosis in children and adolescents.

OBJECTIVE: Increased permeability of the cerebral microvasculature occurs during the treatment of diabetic ketoacidosis (DKA). Microvascular changes consistent with diabetic retinopathy have been reported prior to and after the treatment of DKA. This study evaluated the structural and functional aspects of the retina immediately following the correction of DKA. METHODS: Seven young patients had comprehensive ophthalmologic examinations, including fluorescein angiography, within 24 h after the correction of severe DKA (pH <7.2). RESULTS: None of the patients had clinical, photographic, or angiographic evidence of a retinal abnormality. CONCLUSION: The blood-retinal barrier (BRB) does not experience the same degree of perturbation as the blood-brain barrier (BBB) does and may be a protected site during the insult of DKA and its treatment. The greater stability of the retinal microvasculature may be due to the increased number of pericytes in the BRB in comparison with the BBB.

Adolescent↗
PubMedDate not supplied

The macular xanthophylls.

The macular pigments are predominantly composed of three carotenoids: lutein, zeaxanthin, and meso-zeaxanthin. These carotenoids are concentrated and distributed in a selective manner. The properties of these pigments are further explored along with their methods of uptake, stabilization, and storage. The dual nature of these pigments as filters and antioxidants are elaborated upon in relation to their protective effects upon the macula, specifically in age-related macular degeneration. Evidence suggests that increased levels of macular pigment are correlated with a decreased risk of age-related macular degeneration. Many have sought to exploit this therapeutic relation. Studies reveal that oral supplementation with lutein and zeaxanthin can increase the levels of macular pigments in the retina and plasma. The effects of such supplementation on actual ocular function have yet to be fully addressed. New and standardized methods of assessing macular pigment density are discussed and future areas of research to further our understanding of macular xanthophylls as they pertain to age-related macular degeneration are highlighted.

Humans↗
PubMedDate not supplied

Spontaneous resolution of optic nerve coloboma-associated retinal detachment.

We report a congenital neurosensory retinal detachment associated with an optic nerve coloboma with subsequent spontaneous reattachment. This represents the earliest reported case of such a clinical situation. An observation period is recommended for infants with this clinical course to allow for the opportunity of spontaneous reattachment.

Coloboma↗