ABSTRACT
PURPOSE: Although several studies have reported imaging findings associated with idiopathic intracranial hypertension (IIH), less is known about the correlation between imaging findings and IIH-related symptoms or signs. Our study aimed to determine if clinical features of IIH are correlated with magnetic resonance imaging (MRI) features. METHODS: A retrospective chart review was conducted on consecutive patients presenting at the neuro-ophthalmology department over the last 15 years. All patients diagnosed with IIH were identified and those with available MRI were included in the final analysis. All MRI images were reviewed by a neuroradiologist blinded to the presenting symptoms and signs. Statistical analysis was performed to determine the correlation between the MRI findings with each clinical symptom or sign. RESULTS: Thirty-one out of 88 patients with the initial diagnosis of IIH had MRI available and were included in the study. Significant correlations were observed between colour vision and amount of perineural fluid around the optic nerve on MRI (r = - 0.382; p = 0.004), disc assessment and intraocular optic nerve protrusion (r = 0.364; p = 0.004), disc assessment and perineural fluid around the optic nerve (r = 0.276; p = 0.033) and disc assessment and venous sinus stenosis (r = 0.351; p = 0.009). CONCLUSION: Our study highlights correlations between imaging and clinical findings of IIH. MRI findings in IIH may be useful in ruling out ominous causes of intracranial pressure and risk stratifying ophthalmologic intervention and management of patients with headaches possibly due to IIH.
Subject(s)
Magnetic Resonance Imaging , Pseudotumor Cerebri/diagnostic imaging , Adolescent , Female , Humans , Male , Pseudotumor Cerebri/complications , Radiography , Reproducibility of Results , Retrospective Studies , Symptom Assessment , Young AdultABSTRACT
The purpose of this study was to investigate whether an electrically guided needle insertion technique would enable greater success at intratracheal needle tip insertion than the traditional, aspiration-of-air technique. Twenty-seven anaesthesiology residents were assessed in their ability to place a needle tip in the trachea of cadavers using the two methods. Success of needle placement, time to placement and confidence in placement were recorded. Correct intratracheal needle placement was achieved by 22% of residents (6/27) using the aspiration-of-air method vs 82% (22/27) using the electrically guided method (p<0.001). For the instances of success, there was no significant difference between the two methods in the median (IQR [range]) time taken (28 (24-49 [18-63]) s aspiration vs 32 (19-49 [15-84]) s electrical; p=0.93). The electrically guided method provides an acceptably quick and accurate way of placing a needle tip into the tracheal lumen and can be learnt easily by anaesthesiology residents.
Subject(s)
Anesthesiology/education , Cadaver , Needles , Trachea/anatomy & histology , Clinical Competence , Electronics , Female , Fiber Optic Technology , Humans , Internship and Residency , Reproducibility of ResultsABSTRACT
A new method, non-Markovian quantum-classical approximation (NQCA), is suggested to model the photoisomerization of polyatomic molecules. The NQCA method can be successfully applied to follow the photoisomerization process for a wide class of reacting systems, namely, those for which the time scale required for the equilibration in the phase space of the potential energy surface (PESs) is short compared to the time scale of the transitions between them. Such a situation is quite typical for the nonadiabatic transitions between the different electronic states in polyatomic molecules, where a high density of vibronic states facilitates the intramolecular vibrational energy redistribution, thus providing an efficient relaxation for the phase space distribution. The NQCA can easily be combined with molecular dynamics and quantum-chemical methods to describe the evolution of the classical degrees of freedom and the quantum part of the problem.
Subject(s)
Coumaric Acids/chemistry , Photochemical Processes , Quantum Theory , Stilbenes/chemistry , Absorption , Isomerism , Light , Models, Molecular , Molecular Conformation , ThermodynamicsABSTRACT
Hot absorption spectra of polyatomic molecules may exhibit a characteristic shoulder. Its origin and connection to the 0-0 transition energy gap has been established on the basis of a recently developed quantum-classical approach. We demonstrate that an accurate estimate of the transition energy can be obtained directly from experimental data. The method can be used to study the solvent influence on the energetics of electronic transitions.
Subject(s)
Hot Temperature , Solvents/chemistry , Spectrophotometry , Quantum Theory , Stilbenes/chemistry , Tyrosine/chemistryABSTRACT
Migration has become a profound global phenomenon in this century. In Canada, uncoordinated policies, including those related to immigration, resettlement, employment, and government funding for health and social services, present barriers to immigrant women caregivers. The purpose of this paper is to share relevant insights from individual and group interviews with immigrant women family caregivers, service providers and policy influencers, and discuss these in relation to immigration, health and social policy, and programme trends in Canada. The present authors conducted individual interviews with immigrant women family caregivers (n = 29) in phase 1, followed by two group interviews with women family caregivers (n = 7), and two group interviews with service providers and policy-makers (n = 15) in phase 2. Using an inductive approach, the authors employed thematic content data analysis. Immigrant women experienced barriers to health and social services similar to Canadian-born family caregivers, particularly those who have low incomes, jobs with limited flexibility and heavy caregiving demands. These immigrant women family caregivers avoided certain formal services for a variety of reasons, including lack of cultural sensitivity. However, their challenges were compounded by language, immigration and separation from family in the home country. The identified barriers to support reinforce the importance of modifying and expanding policies and programmes affecting immigrant women's ability to care for family members with illnesses or disabilities within the context of Canadian society. Participants recommended changes to policies and programmes to deal with information, transportation, language, attitudinal and network barriers. The various barriers to services and programmes which were experienced by immigrant women caregivers underscore the importance of reviewing policies affecting immigration, caregiving, and access to health and social services. Intersectoral collaboration among agencies is essential to reduce the barriers identified in the present study, and to establish services which are linguistically and culturally appropriate.
Subject(s)
Caregivers , Emigration and Immigration , Health Services Accessibility/organization & administration , Social Work/organization & administration , Women , Asian People , Canada , Female , Health Policy , Humans , Socioeconomic FactorsABSTRACT
A generalization of the recently published quantum-classical approximation [A. A. Neufeld, J. Chem. Phys., 119, 2488 (2003)] for the purposes of reaction dynamics in condensed phase is presented. The obtained kinetic equations treat a solvent influence in a nonphenomenological way, account for the change of the free energy of the surrounding media, allow for different solvent dynamics in each reaction channel, and constitute a powerful framework for an accurate modeling of solvent effects, including ultrafast processes. The key features of the approach are its differential form, which considerably facilitates practical applications, and well defined wide applicability limits. The developed methodology fully accounts for an arbitrary long memory of the canonical bath and covers solvent-induced processes from a subpicosecond time scale.
Subject(s)
Solutions/chemistry , Solvents/chemistry , Kinetics , Molecular Conformation , Quantum Theory , ThermodynamicsABSTRACT
Based on results of the preceding paper, and assuming fast equilibration in phase space to the temperature of the surrounding media compared to the time scale of a reaction, we formulate a statistical theory of intramolecular nonadiabatic transitions. A classical mechanics description of phase space dynamics allows for an ab initio treatment of multidimensional reaction coordinates and easy combination with any standard molecular dynamics (MD) method. The presented approach has several features that distinguishes it from existing methodologies. First, the applicability limits of the approach are well defined. Second, the nonadiabatic transitions are treated dynamically, with full account of detailed balance, including zero-point energy, quantum coherence effects, arbitrarily long memory, and change of the free energy of the bath. Compared to popular trajectory surface hopping schemes, our MD-based algorithm is more efficient computationally, and does not use artificial ad hoc constructions like a "fewest switching" algorithm, and rescaling of velocities to conserve total energy. The enhanced capabilities of the new method are demonstrated considering a model of two coupled harmonic oscillators. We show that in the rate regime and at moderate friction the approach precisely reproduces the free-energy-gap law. It also predicts a general trend of the reaction dynamics in the low friction limit, and is valid beyond the rate regime.
ABSTRACT
A fully classical limit of the recently published quantum-classical approximation [A. A. Neufeld, J. Chem. Phys. 119, 2488 (2003)] is obtained and analyzed. The resulting kinetic equations are capable of describing the evolution of an open system on the entire time axis, including the short-time non-Markovian stage, and are valid beyond linear response regime. We have shown, that proceeding to the classical mechanics limit we restrict the class of allowed correlations between an open system and a canonical bath, so that the initial conditions and the relaxation operator has to be appropriately modified (projected). Disregard of the projection may lead to unphysical behavior, since mechanism of the decay of some correlations is essentially of quantum-mechanical nature, and is not correctly described by classical mechanics. The projection (quantum correction to the kinetics) is particularly important for the non-Markovian regime of relaxation towards canonical equilibrium. The conformity of the developed method to the conventional approaches is demonstrated using a model of Brownian motion (heavy particle in the bath of light ones), for which the obtained non-Markovian equations are reduced to the standard Fokker-Planck equation in phase space.
Subject(s)
Models, Chemical , Models, Molecular , Quantum Theory , Computer Simulation , Kinetics , MotionABSTRACT
BACKGROUND: Most research has viewed social support as unconditionally positive, but negative interactions such as conflict and dissatisfaction with support are present in caregivers' relationships and have a negative impact on their health. PURPOSE: The purpose of this study was to describe women's experience of nonsupport and identify the types of nonsupport present in their relationships with family and friends while caring for a family member with dementia. ETHICS: The study received ethical clearance from the university ethics review committee. METHODS: The theoretical perspective of symbolic interaction guided this longitudinal qualitative research. Included in the study were 25 in-depth interviews with a group of eight women selected from a larger study of family caregiving because they described nonsupport in their relationships with family and friends. FINDINGS: The women experienced two types of problems in realizing support. Unmet expectations for support was the most pervasive difficulty and included unfulfilled or missing offers of assistance, unmet expectations for social interaction, mismatched aid, or incompetence on the part of the potential helper. Negative interactions, particularly with kin, took several forms: disparaging comments that belittled a caregiver's experience, conflict between the caregiver and others in their appraisal of the care recipient's health status, criticism of the caregiver's decisions in caring for the care recipient, and spillover from longstanding conflict and issues in the family history. LIMITATIONS: This study was limited to women caring for an adult relative with dementia and included a relatively homogeneous sample of English speaking, North American women of European descent. CONCLUSIONS: This study highlighted the utility of identity theory to explain the impact of unmet expectations for support and recognized disparaging comments as a form of nonsupportive interactions.
Subject(s)
Caregivers/psychology , Dementia/nursing , Social Support , Women/psychology , Aged , Attitude to Health , Consumer Behavior , Emotions , Female , Humans , Interpersonal Relations , Middle AgedABSTRACT
The recruitment of articulate, expressive participants is an essential part of methodology in qualitative research. This article presents the authors' experience in the recruitment of immigrant women of Chinese and South Asian origin in an ethnographic study. The study included women caring for an adult or child family member who had a chronic health problem. Knowledge of women family caregivers' health is restricted by the failure to include diverse groups of women in research. In this article, the authors discuss issues related to recruitment and participation of immigrant women in research, including establishing access to diverse groups of women, benefits for immigrant women, and placing the researcher and research process on the same level. Practical research strategies to address these issues and engage the women in research that portrays their perspectives are presented. The authors' discussion concludes with reflection on their experience and that of other researchers.
Subject(s)
Caregivers/psychology , Emigration and Immigration , Family/psychology , Nursing Methodology Research/organization & administration , Patient Acceptance of Health Care/ethnology , Patient Selection , Women/psychology , Adult , Anthropology, Cultural , Asia/ethnology , Attitude of Health Personnel , Canada , Child , China/ethnology , Chronic Disease/nursing , Cultural Diversity , Female , Health Services Accessibility/standards , Humans , Research Personnel/psychology , Social SupportABSTRACT
To investigate the distribution and potential participation of microglia, the resident defense cells of the central nervous system, in the optic nerve head (ONH) in glaucoma, histological paraffin sections of optic nerves from normal and glaucoma patients with mild to advanced nerve damage were studied using double labeling immunohistofluorescence. A monoclonal antibody for HLA-DR, indicating activated microglia, was colocalized with antibodies for functional proteins. In normal ONHs, microglia do not contain TGF-beta2, COX-2, or TNF-alpha and are not positive for PCNA; however, in glaucomatous ONHs, microglia contain abundant TGF-beta2, TNF-alpha, and PCNA. In glaucomatous eyes, a few microglia are usually positive for COX-2. In normal ONHs, there are rarely microglia containing TGF-beta1, NOS-2, TSP, TIMP-2, and CD68, but, in glaucomatous tissue, a few microglia are positive from the prelaminar to the postlaminar regions. MMP-1, MMP-2, MMP-3, and MMP-14 are constitutively present in the perivascular microglia in normal ONHs and appear to be more abundant in glaucomatous tissue. COX-1, TNF-R1, TIMP-1, and c-fms are constitutively present in normal tissues and appear to be increased in microglia in the glaucomatous ONHs. HSP27 is not present in microglia. In glaucomatous ONHs, microglia become activated and phagocytic and produce cytokines, mediators, and enzymes that can alter the extracellular matrix. Our findings suggest that activated microglia may participate in stabilizing the tissue early in the disease process, but, as the severity of the glaucomatous damage increases, the activities of microglia may have detrimental consequences for the pathological course of glaucomatous optic neuropathy.
Subject(s)
Glaucoma/pathology , Microglia/pathology , Optic Disk/pathology , Aged , Aged, 80 and over , Antigens, CD/metabolism , Cyclooxygenase 1 , Cyclooxygenase 2 , Glaucoma/metabolism , Glaucoma/physiopathology , Humans , Immunohistochemistry , Isoenzymes/metabolism , Matrix Metalloproteinases/metabolism , Membrane Proteins , Microglia/metabolism , Middle Aged , Mitosis/physiology , Nitric Oxide Synthase/metabolism , Nitric Oxide Synthase Type II , Optic Disk/metabolism , Optic Disk/physiopathology , Phagocytosis/physiology , Prostaglandin-Endoperoxide Synthases/metabolism , Receptor Protein-Tyrosine Kinases/metabolism , Receptors, Cell Surface/metabolism , Receptors, Tumor Necrosis Factor/metabolism , Receptors, Tumor Necrosis Factor, Type I , Thrombospondins/metabolism , Tissue Inhibitor of Metalloproteinases/metabolism , Transforming Growth Factor beta/metabolism , Transforming Growth Factor beta1 , Transforming Growth Factor beta2 , Tumor Necrosis Factor-alpha/metabolismABSTRACT
An estimated 6.2% of children in the United States satisfy the criteria for a depression diagnosis, but approximately half of this group do not receive necessary treatment. Thus it is important to consider potential barriers to use through service system finance. This article reviews three major types of changes affecting access: parity legislation, managed care, and public contracting. How these developments will affect children with depression and manic depression (DMD) is unclear. To better understand the potential effects on children with DMD, this review uses new data from the Medical Expenditure Panel Survey to describe the service use patterns of this population. These children have higher levels of expenditures, higher rates of inpatient use, and higher rates of Medicaid payment than do other children with mental health diagnoses; they also are overrepresented among the costliest cases of mental illness in children. Children with DMD pay a relatively low out-of-pocket share, suggesting that parity efforts focusing only on copayments and deductibles will have little effect on the absolute out-of-pocket burden for these children. Because children with DMD are overrepresented among high utilizers of health services, health care rationing arrangements or techniques, such as utilization review and capitation, may place this population at particular risk.
Subject(s)
Bipolar Disorder/economics , Depressive Disorder, Major/economics , Insurance, Health/economics , Mental Health Services/economics , Child , Humans , Managed Care Programs/economics , Mental Health Services/supply & distribution , United StatesSubject(s)
Aging/physiology , Diabetes Mellitus, Experimental/physiopathology , Glaucoma/physiopathology , Reperfusion Injury/physiopathology , Retinal Ganglion Cells/physiology , Animals , Body Weight , Cell Survival , Diabetes Mellitus, Experimental/complications , Diet , Energy Intake , Glaucoma/complications , Humans , Intraocular Pressure , Rats , Reperfusion Injury/complications , Risk FactorsABSTRACT
OBJECTIVE: To determine whether astrocytes of the human optic nerve head can induce nitric oxide synthase-2 (NOS-2) in response to elevated hydrostatic pressure as a mechanism for directly damaging the axons of the retinal ganglion cells in glaucoma. METHODS: Primary cultures of astrocytes from human optic nerve heads were placed in chambers, either pressurized at elevated hydrostatic pressure (60 mm Hg) or maintained at ambient pressure. The induction of NOS-2 was studied by immunocytochemistry, immunoblot, and semiquantitative reverse transcription polymerase chain reaction. RESULTS: In astrocyte cultures under ambient pressure, NOS-2 was almost undetectable. In astrocyte cultures under elevated hydrostatic pressure for 24, 48, and 72 hours, intensive labeling of NOS-2 in the Golgi body and the cytoplasm was observed by immunocytochemistry and intense bands of NOS-2 were detected by immunoblotting. As detected by semiquantitative reverse transcription polymerase chain reaction, the messenger RNA level of NOS-2 increased significantly in the astrocytes under elevated hydrostatic pressure within 12 hours, peaking earlier than the protein level of NOS-2. CONCLUSION: Elevated hydrostatic pressure induces the astrocytes of the human optic nerve head to express NOS-2. CLINICAL RELEVANCE: In glaucoma, the appearance of the neurodestructive NOS-2 in astrocytes of the optic nerve head may be a primary response to elevated intraocular pressure, in vivo, and therefore damaging to the axons of the retinal ganglion cells.
Subject(s)
Astrocytes/enzymology , Hydrostatic Pressure , Nitric Oxide Synthase/biosynthesis , Optic Disk/enzymology , Adult , Aged , Astrocytes/cytology , Cells, Cultured , DNA Primers/chemistry , Diffusion Chambers, Culture , Enzyme Induction , Fluorescent Antibody Technique, Indirect , Glial Fibrillary Acidic Protein/metabolism , Humans , Immunoblotting , Middle Aged , Nitric Oxide Synthase/genetics , Nitric Oxide Synthase Type II , Optic Disk/cytology , RNA, Messenger/biosynthesis , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
OBJECTIVE: To investigate the specific cells expressing nitric oxide synthase-2 (NOS-2) in the optic nerve head of patients with primary open angle glaucoma. METHODS: Double-labeling immunohistochemistry was used for labeling of NOS-2 and one of the specific cell markers. RESULTS: NOS-2 was labeled in the astrocytes. The NOS-2 positive astrocytes were mainly located in the damaged area of nerve fibers. A few arteries had NOS-2 labeling in the endothelial cells. There was no significant labeling of NOS-2 in microglia, vascular smooth muscle cells and pericytes. CONCLUSION: In glaucomatous optic nerve neuropathy, NOS-2 is mainly expressed by astrocytes. Astrocytes may play an important role in the local neurotoxicity of axons of the ganglion cells by producing excessive nitric oxide.
Subject(s)
Glaucoma/enzymology , Nitric Oxide Synthase/biosynthesis , Optic Disk/enzymology , Aged , Aged, 80 and over , Humans , Immunohistochemistry , Middle Aged , Nitric Oxide Synthase Type II , Optic Disk/pathologyABSTRACT
Tumor necrosis factor-alpha (TNF-alpha) mediates a range of cellular responses, which have potentially detrimental consequences that affect multiple cell types. To determine whether TNF-alpha contributes to glaucomatous optic neuropathy, we have studied the expression of this cytokine and its receptor, tumor necrosis factor receptor-1 (TNF- R1), in human glaucomatous optic nerve heads from patients with different stages of disease using double labeling fluorescence immunohistochemistry. We have also investigated the ability of this cytokine to induce nitric oxide synthase (NOS-2) in cultured human optic nerve astrocytes by immunocytochemistry and immunoblot. Normal tissue showed constitutive expression of TNF-R1 in the vasculature of the optic nerve heads but no positive labeling for TNF-alpha. In the glaucomatous optic nerve heads, the expression of both TNF-alpha and TNF-R1 were apparently upregulated, primarily in glial fibrillary acidic protein (GFAP)-positive astrocytes, and appeared to parallel the progression of optic nerve degeneration. In eyes with severe glaucomatous damage, some HLA-DR positive microglia also contained TNF-alpha and TNF-R1. In the most severely damaged optic nerve heads, the axons of the retinal ganglion cells contained TNF-R1 and, therefore, are direct targets for neurodegeneration caused by TNF-alpha. In vitro astrocytes constitutively express TNF-R1 and TNF-alpha stimulation induces expression of NOS-2. We hypothesize that TNF-alpha contributes to the progression of optic nerve degeneration in glaucoma by both a direct effect on the axons of the retinal ganglion cells and by inducing NOS-2 in astrocytes.
Subject(s)
Glaucoma/metabolism , Glaucoma/physiopathology , Neuroglia/metabolism , Optic Disk/metabolism , Optic Disk/physiopathology , Optic Nerve Diseases/etiology , Tumor Necrosis Factor-alpha/metabolism , Aged , Aged, 80 and over , Astrocytes/metabolism , Astrocytes/pathology , Cells, Cultured , Glaucoma/pathology , Humans , Middle Aged , Neuroglia/pathology , Neurotoxins/adverse effects , Neurotoxins/metabolism , Nitric Oxide/adverse effects , Nitric Oxide/metabolism , Nitric Oxide Synthase/adverse effects , Nitric Oxide Synthase/metabolism , Nitric Oxide Synthase Type II , Optic Disk/pathology , Optic Nerve Diseases/pathology , Optic Nerve Diseases/physiopathology , Receptors, Tumor Necrosis Factor/metabolism , Retinal Ganglion Cells/metabolism , Retinal Ganglion Cells/pathology , Tumor Necrosis Factor-alpha/adverse effectsABSTRACT
Inducible nitric oxide synthase (NOS-2) is abundantly present in the optic nerve heads of glaucoma patients. To determine the regulation of NOS-2 expression in the glaucomatous optic nerve head, the specific cells that express NOS-2 in the optic nerve heads of patients with primary open-angle glaucoma were studied by immunohistochemical double-labeling of NOS-2 and one of the characteristic cell markers for different cell types. Most of the labeling for NOS-2 was identified in reactive astrocytes that were clustered in the areas of nerve damage in the prelaminar and lamina cribrosa regions of the glaucomatous optic nerve heads. In vitro, the expression of GFAP and NOS-2 by reactive astrocytes of human optic nerve heads was demonstrated by immunocytochemistry and Western blot. In primary cultures of human lamina cribrosa astrocytes, stimulation by interferon-gamma and interleukin-1beta upregulated GFAP and induced expression of NOS-2 protein. At 24, 48 and 72 h of stimulation, NOS-2 appeared first in the Golgi body and then was sent out into the cytoplasm in granules. These results demonstrated that the astrocytes of human optic nerve head are capable of inducing the expression of NOS-2. Reactive astrocytes in the glaucomatous optic nerve heads apparently play an important role in local neurotoxicity to the axons of the retinal ganglion cells by producing excessive nitric oxide in glaucomatous optic neuropathy.
Subject(s)
Astrocytes/enzymology , Glaucoma, Open-Angle/metabolism , Nitric Oxide Synthase/biosynthesis , Optic Nerve/pathology , Aged , Aged, 80 and over , Astrocytes/chemistry , Astrocytes/cytology , Cells, Cultured , Glaucoma, Open-Angle/pathology , Glial Fibrillary Acidic Protein/analysis , Humans , Middle Aged , Nitric Oxide Synthase/analysis , Nitric Oxide Synthase Type II , Retinal Ganglion Cells/pathologyABSTRACT
Reducing health inequities associated with poverty is an important public health nursing role. This article describes the scope of research on the health of low-income Canadian women. The research included was published in English-language peer-reviewed journals between 1990 and 1997. The 26 articles retrieved are summarized according to the focus of the study and the composition of the sample. Most addressed personal health practices and health status. Only one intervention study was identified. The studies and the findings of this analysis are discussed in relation to three recommendations for research on women's health: an emphasis on social context, including the structural conditions affecting women's health; active participation of women in the research process; and recognition of diversity among low-income women. Suggested priority areas for future research are: intervention studies; studies addressing the structural context of the lives of low-income women; research strategies that enhance the participation of women in the research process; and increased involvement of diverse groups of women such as homeless women and women of varied ethnic backgrounds, including First Nations women.
Subject(s)
Health Status , Poverty , Women's Health , Canada , Female , HumansABSTRACT
The neuronal form of nitric oxide synthase (NOS-1) has been localized to several cell types in the retinas of experimental animals; however, localization in the human retina has not been definitive. By using in situ hybridization and immunohistochemistry, we have compared the cellular expression and localization of NOS-1 in the rat and human retinas. In both rat and human retinas, NOS-1 is expressed in the inner segments of photoreceptors, cells in the inner nuclear layer, particularly amacrine cells, and retinal ganglion cells. In human cones, NOS-1 is abundantly present in the outer segments. In the rat, optic nerve transection caused a loss of cells that were positive for NOS-1 in the ganglion cell layer. Although a retinal ganglion cell localization has not been reported consistently in the literature, our data clearly localize NOS-1 to the retinal ganglion cells of the rat and human retinas.
Subject(s)
Nitric Oxide Synthase/metabolism , Photoreceptor Cells/enzymology , Retinal Ganglion Cells/enzymology , Animals , Humans , Immunohistochemistry , In Situ Hybridization , Male , Nitric Oxide Synthase Type I , Optic Nerve Injuries/enzymology , Rats , Retina/enzymologyABSTRACT
PURPOSE: To investigate the hypothesis that nitric oxide (NO) in the optic nerve heads of rats with chronic moderately elevated intraocular pressure (IOP) contributes to neurotoxicity of the retinal ganglion cells, the presence of the three isoforms of nitric oxide synthase (NOS) was determined in the tissue. METHODS: Unilateral chronic moderately elevated IOP was produced in rats by cautery of three episcleral vessels. Histologic sections of optic nerves from eyes with normal IOP and with chronic moderately elevated IOP were studied by immunohistochemistry and by immunoblot analysis. Polyclonal antibodies to NOS-1, NOS-2, NOS-3, and glial fibrillary acidic protein (GFAP) were localized with immunoperoxidase. RESULTS: In the optic nerve of rat eyes with normal IOP, NOS-1 was constitutively present in astrocytes, pericytes and nerve terminals in the walls of the central artery. NOS-2 was not present in eyes with normal IOP. In these eyes, NOS-3 was constitutively present in the vascular endothelia of large and small vessels. Rat eyes treated with three-vessel cautery had sustained elevated IOP (1.6 fold) for at least 3 months. In these eyes, no obvious changes in NOS-1 or NOS-3 were noted. However, at time points as early as 4 days of chronic moderately elevated IOP, NOS-2 appeared in astrocytes in the optic nerve heads of these eyes and persisted for up to 3 months. Immunoblot analysis did not detect differences in NOS isoforms. CONCLUSION: The cellular distributions of constitutive NOS isoforms in the rat optic nerve suggest physiological roles for NO in this tissue. NOS-1 in astrocytes may produce NO as a mediator between neighboring cells. NO, produced by NOS-1 in pericytes and nitrergic nerve terminals and by NOS-3 in vascular endothelia, is probably a physiological vasodilator in this tissue. In eyes with chronic moderately elevated IOP, NOS-2 is apparently induced in astrocytes. The excessive NO production that is associated with this isoform may contribute to the neurotoxicity of the retinal ganglion cells in eyes with chronic moderately elevated IOP.