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1.
Yakugaku Zasshi ; 140(10): 1235-1242, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32999202

RESUMO

The central nervous system (CNS) is segregated from the circulating blood and peripheral tissues by endothelial and epithelial barriers. To overcome refractory CNS diseases, it is important to understand the membrane transport systems of drugs and the endogenous compounds that relate to the pathogenesis of CNS diseases at these barriers. The endothelial barrier in the brain is the blood-brain barrier (BBB). Our studies clarified the efflux transport of prostaglandin E2 (PGE2), a modulator of neural excitation and inflammatory responses, across the BBB via plasma membrane transporters such as organic anion transporter 3 (Oat3) and multidrug resistance-associated protein 4 (Mrp4). This efflux transport was attenuated by peripheral inflammation or cerebral treatment with neuroexcitatory l-glutamate, suggesting that BBB-mediated PGE2 elimination was altered under several pathological conditions. We also examined excitatory amino acid transporter (EAAT) 1 and 3 as l-glutamate efflux transporters of the inner blood-retinal barrier (BRB) and blood-cerebrospinal barrier. It was considered that these efflux membrane transporters participated in the homeostasis of neuroexcitatory and neuroinflammatory responses in the brain and retina. Moreover, we identified connexin 43 (Cx43) hemichannels as a new membrane transport system that is activated under pathological conditions and recognizes several monocarboxylate drugs, such as valproate. As it is expected that the action of these membrane transporters across the CNS barriers is of great importance in understanding the pathology of various neuroexcitatory diseases, our studies should contribute to the establishment of therapeutic strategies for refractory CNS diseases.


Assuntos
Transporte Biológico , Barreira Hematoencefálica/metabolismo , Barreira Hematorretiniana/metabolismo , Encéfalo/metabolismo , Doenças do Sistema Nervoso Central/etiologia , Doenças do Sistema Nervoso Central/metabolismo , Desenvolvimento de Medicamentos , Proteínas de Membrana Transportadoras/metabolismo , Retina/metabolismo , Animais , Doenças do Sistema Nervoso Central/tratamento farmacológico , Conexina 43/metabolismo , Dinoprostona/metabolismo , Transportador 1 de Aminoácido Excitatório/metabolismo , Ácido Glutâmico/metabolismo , Humanos , Camundongos , Terapia de Alvo Molecular , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismo
2.
Beijing Da Xue Xue Bao Yi Xue Ban ; 52(5): 845-850, 2020 Oct 18.
Artigo em Chinês | MEDLINE | ID: mdl-33047717

RESUMO

OBJECTIVE: To investigate the expression efficiency of exogenous gene mediated by different serotypes of adeno-associated virus (AAV) vectors in retina, and to compare the expression efficiency of AAV vector and two kinds of promoters commonly used in ophthalmology after transfection into mouse retina, so as to provide the basis for selecting appropriate AAV vector and promoter for gene therapy of retinitis pigmentosa. METHODS: AAV2/2, AAV2/5, AAV2/8 and AAV2/9 were prepared. The C57BL/6J mice were injected subretinally with 1 µL purified AAV vectors (1.00×1013 mg/L). Then the mice were killed 2 or 4 weeks after treatment, and the eyes were enucleated for frozen section. The expression of green fluorescent protein (GFP) was observed under the confocal microscope. Two kinds of promoters, CMV and CAG, were selectd, and the expression of AAV2/8-GFP-CMV and AAV2/8-GFP-CAG was observed under confocal microscope. RESULTS: No bacterial infection or immune response were seen in the injected mice. 2 weeks after injection, the GFP green fluorescence of AAV2/8 and AAV2/9 in the mouse retina was obvious, which indicated that the GFP green fluorescence of AAV2/8 and AAV2/9 was high after transfection into the mouse retina. In these two serotypes, GFP green fluorescence of AAV2/8 was mainly concentrated in photoreceptor cells while AAV2/8 was expressed in the whole retina, indicating that AAV2/8 was more specific to photoreceptors. Further experiments on AAV2/8 showed that the GFP green fluorescence of the mouse retina was obvious 4 weeks after injection, indicating that the exogenous gene mediated by AAV2/8 could be stably expressed in vivo. For CMV and CAG promoters, CMV promoter was expressed stronger in retinal pigment epithelium (RPE)cells, while CAG promoter was stronger in photorecepters. In photorecepters, CAG promoter was expressed almost the same as CMV promoter, while CMV promoter was stronger in RPE cells. CONCLUSION: AAV vectors could express transgene robustly in retinal cells; Among several AAV serotypes, AAV2/2 and AAV2/5 showed weaker GFP fluorescence than AAV2/8 and AAV2/9. AAV2/9 showed expression in each layer of the retina including ganglion cells. AAV2/8 was more specific for photoreceptor; CAG promoters had higher specificity for photoreceptors than CMV promoters.


Assuntos
Dependovirus , Vetores Genéticos , Animais , Dependovirus/genética , Camundongos , Camundongos Endogâmicos C57BL , Retina , Sorogrupo , Transdução Genética
3.
Vestn Oftalmol ; 136(5): 39-45, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33056962

RESUMO

PURPOSE: To study the long-term clinical and functional outcomes of retinopathy in extremely premature infants. MATERIAL AND METHODS: The study included 42 patients (84 eyes) with retinopathy of prematurity (ROP) at the age of 9-18 years. All patients underwent comprehensive ophthalmological examination, including morphometric (OCT), functional (ERG) and psycho-physical (computer perimetry) methods. RESULTS: A high occurrence of low vision (67%) was revealed in extremely premature children with ROP during school years and adolescence, which depended on the severity of active ROP and the formation of pronounced residual changes in the fundus during the cicatricial phase of the disease, a high occurrence of refractive errors (92%), including high degree myopia (46%), late complications that develop with ROP of any degree (68%), impaired retinal electrogenesis - due to both ROP and deep morphological and functional immaturity of the retina. CONCLUSION: Patients with any degree of cicatricial ROP born in the early stages of gestation and with extremely low body weight need regular complex ophthalmologic examination and lifelong follow-up.


Assuntos
Miopia , Erros de Refração , Retinopatia da Prematuridade , Adolescente , Criança , Humanos , Lactente , Lactente Extremamente Prematuro , Recém-Nascido , Retina/diagnóstico por imagem , Retinopatia da Prematuridade/diagnóstico , Retinopatia da Prematuridade/epidemiologia
4.
Vestn Oftalmol ; 136(5): 109-114, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33056971

RESUMO

Neuroleukemia is a severe complication of hemoblastosis, which manifests as lymphoblastic lesions of the brain and cranial nerves. Isolated damage to one of the cranial nerves is rare. The diagnosis is based on the results of ophthalmoscopy, magnetic resonance imaging of the orbits, and lumbar puncture. Literature describes isolated cases of retinal and/or optic nerve damage in the absence of blast cells in the spinal fluid. These are the most difficult situations for timely diagnosis of neuroleukemia. The article describes a patient with MALT lymphoma transformed into diffuse B-large cell lymphoma manifesting as leukemic infiltration of the optic nerve and retina without brain damage and absence of blast cytosis in the spinal fluid. The diagnosis of neuroleukemia was established based on the results of cytological examination of the punctate of the infiltrated peripapillary retina and confirmed by regression of changes in the fundus against the background of antitumor treatment. The vital prognosis for patients with neuroleukemia is unfavorable. However, early diagnosis of leukemic infiltration of the optic nerve and/or retina can restore visual acuity of the affected eye and significantly improve the quality of life.


Assuntos
Linfoma de Zona Marginal Tipo Células B , Humanos , Recidiva Local de Neoplasia , Nervo Óptico , Qualidade de Vida , Retina
5.
Vestn Oftalmol ; 136(5): 116-122, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33056972

RESUMO

Vascular disorders account for a significant proportion of acute loss of vision. In recent years, scientific and technical progress in ophthalmology has provided new opportunities in the study of vascular pathology, significantly expanding the understanding of their pathogenesis. The article presents a clinical case of a patient with acute retinal ischemia syndrome who had retinal blood flow disturbances studied using optical coherence tomography (OCT) imaging. It demonstrates extensive possibilities of diagnostics of ischemic retinal lesions using OCT angiography that make this method the most informative in terms of evaluating the blood flow at different levels, independently in each vascular plexus.


Assuntos
Doenças Retinianas , Vasos Retinianos , Angiofluoresceinografia , Humanos , Retina , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência Óptica
6.
Klin Monbl Augenheilkd ; 237(10): 1187-1193, 2020 Oct.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-33059378

RESUMO

In recent years, an increasing incidence of laser pointer-associated retinal injuries has been observed, likely due to easy access to incorrectly classified laser pointers, their labelling as toys, and lack of awareness concerning the associated risk. Laser pointer exposure can lead to irreversible retinal damage and associated vision loss, depending on the wavelength, radiation power, duration of exposure, localization, and spot size. Pronounced retinal laser damage is especially seen in children and teenagers. The structural appearance of retinal laser pointer damage varies and, in some cases, may be a diagnostic challenge. Besides often subtle findings on optical coherence tomography examination, characteristic alterations on near-infrared autofluorescence imaging may be valuable for the diagnosis of retinal laser pointer injuries and for differentiating other retinal lesions with similar appearance. The increase in laser pointer injuries indicates that regulatory actions and increased public awareness are required regarding the dangers of laser pointers.


Assuntos
Retina , Doenças Retinianas , Adolescente , Criança , Humanos , Lasers , Retina/diagnóstico por imagem , Doenças Retinianas/etiologia , Tomografia de Coerência Óptica , Acuidade Visual
7.
Klin Monbl Augenheilkd ; 237(10): 1225-1229, 2020 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-33059379

RESUMO

One of the most controversial discussions in retinal surgery is currently being held about the importance of intraoperative OCT (iOCT). The background is the desire to combine the 2-dimensional fundus view of the surgeon with the layered depth information of OCT to achieve a 4-dimensional "augmented reality" (3-D plus change over time). This should help to visualise fine structures, which have been hidden from the surgeon's view. Therefore, retinal surgery seems to be predestined for the use of iOCT. The great hope is that a dynamic live 3-D image with real-time feedback will provide the surgeon with additional information and improve safety. Although fascinating at the first glance, in the surgical routine, however, iOCT technology is disappointing, especially in macular surgery. It rarely provides substantial information that would not be obtainable without iOCT or that would not be available in much better quality through preoperative diagnostic testing. Only some special indications remain, particularly related to subretinal surgery.


Assuntos
Retina , Tomografia de Coerência Óptica , Fundo de Olho , Procedimentos Cirúrgicos Oftalmológicos , Retina/diagnóstico por imagem , Retina/cirurgia , Corpo Vítreo
8.
Vestn Oftalmol ; 136(4. Vyp. 2): 183-192, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32880138

RESUMO

PURPOSE: To evaluate the relationship between the morphological and functional parameters of retinal pigment epithelium (RPE) and photoreceptors (PR) in inherited retinal diseases (IRD). MATERIAL AND METHODS: The study included 52 patients (104 eyes), 23 of them with Stargardt Disease (STGD), 19 with cone-rod dystrophy (CRD), 10 with retinitis pigmentosa/pigmentary abiotrophy (RP) of comparable disease durations. All patients underwent standard and additional ophthalmological examination: fundus autofluorescence (AF), spectral optical coherence tomography (OCT), computer perimetry (CP), electro-oculography (EOG), Ganzfeld electroretinography (gERG). RESULTS: Comparison of the groups of IRD patients and groups according to the degree of RPE damage with the control group revealed an increase in differences in the EOG and gERG indicators as the area and depth of damage to the RPE and PR progressed. The patterns of changes in RPE and PR, the frequency of their occurrence with IRD in this patient sample are described. A moderate correlation was found between the amount of RPE loss and EOG light rise, as well as between the defect of the ellipsoid zone and the amplitude of α- and ß-waves, the latency of ß-wave of the gERG. Some patients showed a mismatch between a small defect of the ellipsoid zone and RPE with significant damage to the visual field and reduction of the EOG and gERG indicators. The obtained electrophysiological indicators revealed pathological changes in RPE and PR, more significant and widespread in some cases than it was shown with visualization methods. Weak and moderate correlations between visual acuity, and RPE damage and light sensitivity index with loss of ellipsoid zone were calculated. CONCLUSIONS: Modern methods of retinal examination can help obtain complete and versatile picture of morphological and functional state of the retina in IDR that supplement each other. EOG and gERG have capability to determine the degree of RPE and PR functions impairment including those cases when morphological studies are not sufficiently informative.


Assuntos
Epitélio Pigmentado da Retina , Retinite Pigmentosa , Eletrorretinografia , Angiofluoresceinografia , Humanos , Retina , Tomografia de Coerência Óptica
9.
Vestn Oftalmol ; 136(4. Vyp. 2): 226-234, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32880144

RESUMO

The article describes a clinical case of acute macular neuroretinopathy and «chronic¼ paracentral acute middle maculopathy in a patient with atypical hemolytic-uremic syndrome - an orphan disease characterized by systemic thrombosis in the vessels of the microcirculatory bed due to chronic uncontrolled activation of the alternative complement pathway. Optical coherence tomography angiography data confirm the ischemic nature of the disease with localization in the deep vascular plexus of the retina in acute macular neuroretinopathy and in the superficial vascular plexus of the retina in «chronic¼ paracentral acute middle maculopathy. The use of modern diagnostic methods, including optical coherence tomography angiography, can help improve detection of the pathology and expand its understanding in severe microangiopathic syndromes, which include atypical hemolytic-uremic syndrome.


Assuntos
Síndrome Hemolítico-Urêmica Atípica , Doenças Retinianas , Angiofluoresceinografia , Humanos , Microcirculação , Retina , Tomografia de Coerência Óptica
10.
Vestn Oftalmol ; 136(4. Vyp. 2): 243-250, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32880146

RESUMO

PURPOSE: To identify the specifics of structural and functional changes in patients with toxic optical neuropathy caused by acute methanol poisoning. MATERIAL AND METHODS: One female patient with toxic optic neuropathy (TON), 2 male patients with partial optic atrophy caused by methanol poisoning, and 1 male patient with methanol intoxication after ethanol containing alcohol use were examined with kinetic perimetry and optical coherence tomography. RESULTS: Patients with TON caused by acute methanol poisoning were observed to have decreasing visual acuity to the extent of complete blindness. OCT follow-up studies revealed thinning of the retinal nerve fiber layer (RNFL) as well as formation of microcysts in the inner retinal layers, destruction of ellipsoid zone and outer segments of photoreceptors. The patient with methanol intoxication after use of ethanol containing alcohol had retained his visual functions; he was found to have microcysts and RNFL thinning during the first few months after the intoxication, but they were within normal range of OCT parameters. CONCLUSION: Patients with TON caused by acute methanol poisoning are common to have optic atrophy with either residual visual functions or complete blindness as well as microcysts formation, structural changes and destruction of the ellipsoid zone and outer segments of photoreceptors. In patient with methanol intoxication after use of ethanol, which is known to be an antidote, complete visual recovery was observed, although some microcystic changes and ganglion cells layer thinning were noted.


Assuntos
Metanol , Células Ganglionares da Retina , Feminino , Humanos , Masculino , Nervo Óptico , Retina , Tomografia de Coerência Óptica , Neuropatia Óptica Tóxica
11.
Vestn Oftalmol ; 136(4. Vyp. 2): 251-257, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32880147

RESUMO

The review addresses the current state of atomic force microscopy (AFM) usage in ophthalmology. Briefly presented here are the history of the development of AFM, principles and modes of operation, its advantages, disadvantages, as well as a comparison with other types of microscopy. The review describes the capabilities of AFM in visualization of various structures of the eye. A significant part of the review is devoted to the study of the retina, which arouses great interest among researchers. In particular, the possibilities of AFM for visualization at the submicron level of various structures in the retina, such as the internal limiting membrane, membrane cells, Müller cells, retinal pigment epithelium in their normal state and in the presence of a pathology (age-related macular degeneration, diabetes mellitus) were reviewed. In addition, several study papers were analyzed, providing a base for the judgement of the mechanical properties of said structures. An AFM study of the visual pigment rhodopsin helped identify its dimeric structure. The stability of the rhodopsin molecule was proved to be determined by the degree of strength of its individual segments connected to each other. The AFM method is a highly accurate method that helps solve many fundamental and practical problems, particularly in ophthalmology.


Assuntos
Oftalmologia , Retina , Microscopia de Força Atômica , Rodopsina
12.
Vestn Oftalmol ; 136(4. Vyp. 2): 272-278, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32880150

RESUMO

Diabetic retinopathy (DR) is an important, socially significant complication of diabetes mellitus that leads to irreversible loss of vision. This article reviews the studies of peripheral changes in DR, different methods used in its diagnostics, monitoring and assessment of therapeutic effects. The article contains detailed examination of the modern widefield imaging methods that allow studying the middle and extreme periphery of the retina and help obtain a wide range of DR biomarkers. Of greatest interest in this matter is optical coherence tomography angiography due to possibility of detailed non-invasive assessment of the condition of retinal microvasculature, precise determination of the area and visualization of the sites of neovascularization and non-perfused regions of the retina. Quantitative characteristics of these changes serve as important diagnostic and prognostic visual biomarkers of DR.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Angiofluoresceinografia , Humanos , Retina , Vasos Retinianos , Tomografia de Coerência Óptica
13.
Vestn Oftalmol ; 136(4. Vyp. 2): 296-299, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32880154

RESUMO

Retinitis pigmentosa (PR) is manifested by decreased vision, night blindness and narrowing of the visual field. In RP, the level of docosahexaenoic acid (DHA) in blood plasma and red blood cells is significantly reduced. The largest amount of DHA is contained in the retina (30-40% of phospholipids). DHA increases membrane permeability, accelerates the release of vital proteins and retinal enzymes, provides differentiation of photoreceptors, and slows down apoptosis. The introduction of DHA in isolation or in combination with other fatty acids into the body increases its concentration and can be used for metabolism. While there is a known correlation between the level of DHA in the blood and certain retinal functions (visual acuity, light sensitivity, the value of bioelectric potential), many years of multicenter studies have not produced reliable data on the direct effect of isolated or combined use of DHA in maintaining retinal functions in PR. Despite inconsistent outcomes, the clinical trials should continue.


Assuntos
Retinite Pigmentosa , Campos Visuais , Ácidos Docosa-Hexaenoicos , Eletrorretinografia , Humanos , Retina , Acuidade Visual
14.
Vestn Oftalmol ; 136(4. Vyp. 2): 300-309, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32880155

RESUMO

The incidence of diabetes in the world is steadily increasing, and so is growing the number of cases of vision loss and blindness resulting from diabetic retinopathy (DR). This pathology is asymptomatic in the initial stages, but only the early treatment can be effective. In this regard, DR screening is an important and actual problem. This article reviews the principles, criteria, and problems of the currently run DR screening programs that are based on digital photography of the fundus. Special attention is paid to the displayed biomarkers and their role in DR screening. Various research methods are described, such as fluorescence angiography, optical coherence tomography, optical coherence tomography agniography, laser scanning ophthalmoscopy, which can be used to visualize pathological changes in the retina associated with DR. These changes were considered as potential screening biomarkers for DR. The review also describes new areas of screening based on telemedicine, artificial intelligence, and mobile photo-registering devices.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Inteligência Artificial , Humanos , Retina , Tomografia de Coerência Óptica
15.
Vestn Oftalmol ; 136(4. Vyp. 2): 367-372, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32880163

RESUMO

The article provides a detailed review of the ophthalmoscopic picture, optical coherence tomography (OCT) of the retina and fundus autofluorescence in patients with such rare pathological processes in the fundus as torpedo maculopathy, retinal myelin fibers, retinal astrocytic hamartoma and cavernous hematoma.


Assuntos
Hamartoma , Doenças Retinianas , Angiofluoresceinografia , Humanos , Retina , Tomografia de Coerência Óptica
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