[Electroretinographic signs of retinal remodeling after experimental induction of retinal pigment epithelium atrophy]. / Elektroretinograficheskie priznaki remodelirovaniya setchatki posle induktsii atrofii retinal'nogo pigmentnogo epiteliya v eksperimente.

Various animal models of atrophy of retinal pigment epithelium (RPE) are created in order to study certain aspects of geographical atrophy in humans. To study the effects of new methods of therapy, it is necessary to determine the objective functional markers of structural changes in the retina. PURPOSE: To determine the alterations in activity of the retina that characterize its remodeling in induction of RPE atrophy. MATERIAL AND METHODS: Full-field electroretinograms (ERG), pattern ERG, and multifocal ERG were recorded according to the ISCEV standards from the right eyes of twenty rabbits of the New Zealand albino breed 6-7 weeks after induction of RPE atrophy by subretinal administration of 0.9% sodium chloride or bevacizumab solution. RESULTS: Characteristic electroretinographic signs of RPE atrophy and retinal remodeling are described. Changes in ERG indicate a predominant inhibition of the functional activity of photoreceptors compared with bipolar cells, which objectively reflects an impairment of their metabolism associated with RPE pathology. With the injection of bevacizumab, a sharp weakening of the functional symbiosis of Mueller cells with bipolar cells was observed. According to pattern ERG, the function of the retinal ganglion cells was reduced. The reaction of the paired eyes after induction of RPE atrophy included a moderate decrease in the amplitude of b-wave of photopic ERG and activation of glia-neuronal relationships. CONCLUSION: Subretinal injections of 0.9% sodium chloride and bevacizumab trigger changes in the retina that reflect specific remodeling of retinal neurons of the second and third orders, which characterizes the used models of RPE atrophy.

[Amplitude-frequency characteristics of the retina under diffuse and pattern stimulation and new formalized signs of flicker and pattern electroretinogram]. / Amplitudno-chastotnye kharakteristiki setchatki pri diffuznoi i pattern-stimuliatsii i novye formalizovannye priznaki ritmicheskoi i pattern- élektroretinogramm.

The clinical sugnificance of electroretinogram interpretation depends heavily on the employed mathematical apparatus. Currently, conventional calculation of the amplitude and time parameters of electroretinogram (ERG) components and their relations (indices), as well as analysis of the frequency spectrum of the signal are becoming insufficient for interpretation of the obtained data. New approaches to diagnostics are currently being developed, using, among other things, expert systems, and neural network and simulation models. PURPOSE: To obtain additional formalized signs of ERG responses to flicker and pattern stimuli by analyzing the amplitude-frequency characteristics of the retina. MATERIAL AND METHODS: A photopic flicker ERG (FERG) and a transient pattern ERG (PERG) were recorded from healthy individuals and patients with glaucoma. Using the digitized FERG and PERG signals, the amplitude-frequency characteristics of the retina were studied. The results of diffuse and structured stimulation modeling in Matlab Simulink were used to identify the characteristics of retinal responses to rhythmic and pattern stimuli. RESULTS: The amplitude-frequency characteristics (AFC) of the retina were obtained for the first time. They objectively reflect its ability to convert spectra of stimulating signals into spectra of recorded ERG responses. Using the results of modeling, diffuse flicker and pattern stimuli we have identified features of retinal response in Matlab Simulink. Based on a simplified simulation model, a negative component (baseline drift) was detected in a healthy person's PERG and its effect on the results of retinal AFC evaluation was investigated. Polynomial approximation procedure of retinal AFC was performed for the first time allowing the use of coefficients of approximating polynomials as new formalized signs in diagnostics. CONCLUSION: AFC were shown to be an objective characteristic of retinal transfer properties, which depend on the type of stimuli acting on it, as well as on the etiology of the retinal disease.

[Functional examinations of visual channels: clinical aspects]. / Funktsional'nye issledovaniia zritel'nykh kanalov: klinicheskie aspekty.

The review discusses literature data on the clinical relevance of functional assessment of magno- (M), parvo- (P), and koniocellular (K) pathways. It also covers the differential contribution of the M, P, and K channels to visual impairments and how it determines the prognosis, early diagnosis, and treatment choice in patients with neurodegenerative diseases of the retina and brain. Selective changes in the performance of the visual channels are investigated by the example of glaucoma and optic neuritis in multiple sclerosis (MS) patients. A detailed analysis of pattern electroretinogram and visual evoked potentials in response to pattern stimuli of varying luminance and chromatic contrast in glaucoma and MS and characteristic functional alterations (objective markers of pathology of the visual pathways) are presented.

[Functional examinations of visual channels: physiological basis]. / Funktsional'nye issledovaniya zritel'nykh kanalov: fiziologicheskie osnovy.

In this paper, technical details of visual evoked potentials (VEP) assessment and pattern electroretinography (PERG) are reviewed. Both methods are used to perform an objective functional examination of visual channels and to clarify the level, at which they have been damaged. Contributions of parvo- (P), magno- (M) and koniocellular (K) systems to the morphology of PERG and VEP responses are discussed with account to test conditions, selectively supportive of the activity of particular cell populations. The review analyzes the physiological role of such stimulation parameters as brightness and color contrast of the pattern elements as well as spatial and temporal frequency in detecting dysfunction of color channels and mistuning of the P- and M- pathways. Different times taken for neuronal integration and signal conduction along the M- and P- pathways determine the timing of the P- and M- VEP components, allowing us to judge their contribution to VEP morphology from the same recording.

[Distinctive morphological and functional changes in retinal ganglion cells associated with normal aging and early stage of glaucoma]. / Morfofunktsionalnye osobennosti izmeneniya ganglioznykh kletok setchatki pri fiziologicheskom starenii i v rannei stadii glaukomy.

UNLABELLED: Early diagnosis of primary open-angle glaucoma (POAG) is closely connected with detection of normal age-related changes in the retina. It is also essential to develop reliable methods for quantitative evaluation of retinal nerve fiber layer (RNFL) thickness and retinal ganglion cells (RGCs) structure and function as well as to extend opportunities for inter-instrumental comparisons. AIM: to assess the function of RGCs from parvo- and magnocellular pathways by means of pattern electroretinography and to evaluate the degree of retinal sensitivity loss and RNFL thickness using new methods of analysis in normal aging and the early stage of POAG. MATERIAL AND METHODS: Four groups were formed: group 1 - young healthy participants, group 2 - aged controls, group 3 - glaucoma suspects, and group 4 - early-stage POAG patients. In all groups we investigated the MD and PSD indices of static computer perimetry (HEP, Heidelberg Edge Perimeter, SAP and FDF tests) and RNFL thickness provided by HRT III (Heidelberg Engineering). Pattern electroretinograms (PERGs) were recorded with the RETImap system (Roland Consult) at the check sizes of 0.8° and 16°. For steady-state and transient PERGs the 0.8°/16° and N95/P50 ratios were calculated, respectively. RESULTS: There was a statistically significant difference in PERG amplitudes to 0.8° checks (p=0.0001) and in 0.8°/16° ratios (p=0.0001) between the groups 1 and 2. Differences between the groups 2 and 3 as well as 3 and 4 were statistically significant only as to 0.8° checks (p=0.03 and p=0.001, respectively). Responses to 16° checks were alike in all groups. We have also applied original formulas to determine the relative loss of RGCs and their axons and the congruence coefficient for morphological and functional parameters in normal aging and the early stage of POAG. CONCLUSION: The discovered age-related PERG changes convincingly indicate a greater parvocellular RGC loss as compared to magnocellular. Thus, the PERG ratio (0.8°/16°) should be corrected for the subject's age. The proposed indices of relative decline in retinal light sensitivity and RNFL thinning have been shown to be useful for quantifying the loss of RGC bodies and axons in normal aging and early-stage glaucoma.

[Alterations of physiological rhythms in neurodegenerative disorders: problems and prospects of light therapy].

This review provides an outline of circadian disorders associated with neurodegenerative diseases of the brain in the elderly, including Alzheimer's (AD) and Parkinson's diseases (PD). Since light is one of the most powerful environmental cues synchronizing physiological rhythms, exposure to bright light is often used to treat sleep disorders, behavior of patients with severe dementia, gait, and other functions disordered in CNS pathologies. Photobiomodulation effects of the low-energy laser and LED radiation is also considered as a potential tool for the rehabilitation of patients with various pathologies. It yielded positive results in the treatment of both PD and AD. An external factor that can exacerbate a course of neurodegenerative diseases is light pollution. Irrational artificial lighting can cause jet lag, affect visual and cognitive functions. The review also summarizes the current understanding of fractal dynamics of physiological rhythms in healthy subjects (including brain activity) and their reduced complexity in pathological conditions. The loss of multiscale complexity of brain electrical activity has been documented for patients with AD, PD, epilepsy, and schizophrenia. It is thought to reflect fundamental changes in the regulation of the body's circadian rhythms. Recently, M.V Zueva proposed and theoretically substantiated the hypothesis that allows taking another look at the prospects for the use of light stimulation. It is expected that the use of stimuli with fractal structure can help to restore the retina and brain's functions in neurodegenerative diseases by reactivation of neuronal plasticity and be an innovative method for the treatment of neurodegenerative disorders.

[Electrophysiological evaluation of retinal function after systemic and superselective intra-arterial chemotherapy for retinoblastoma].

Since the prognosis for visual acuity after polychemotherapy or superselective intra-arterial chemotherapy (SIACT) is doubtful, studying retinal function in children with retinoblastoma by means of clinical electroretinography (ERG) is a relevant issue. The latter enables objective post-treatment assessment of retinal function and evaluation of possible infusion-related retinal toxicity. This review analyzes ERG findings in children with retinoblastoma treated with chemotherapy, including SIACT.

[Evoked retinal and cortical potentials in children with advanced and resistant retinoblastoma after neoadjuvant polychemotherapy and superselective intra-arterial chemotherapy].

Electrophysiological examinations (in accordance with the ISCEV Standards and original protocols) were performed after neoadjuvant chemotherapy or before and after superselective intra-arterial chemotherapy (SIACT) in 18 children aged 1-3 years with either newly diagnosed advanced retinoblastoma (8 eyes) or resistant retinoblastoma (14 eyes). The most considerable decrease in amplitude was demonstrated by the cone response b-wave, photopic 24 Hz flicker electroretinogram (ERG), photopic negative response, and the P1-component of multifocal ERG, indicating a significant dysfunction of bipolar and ganglion cells, more pronounced in the macular zone. After the SIACT, central retinal functions improved. In eyes with retinoblastoma there is a moderate peak latency shortening of the flash visual evoked potential (VEP) P2-component, which reflects functional changes in the central retina rather than those in the visual pathways, and therefore, flash VEP analysis is a useful tool of chemotherapy patient monitoring, especially when electroretinography cannot be performed.

[Fundamental ophthalmology: the role of electrophysiological studies].

Studying of functional aspects of eye disease pathogenesis by electrophysiological methods is widely demanded in fundamental ophthalmology. Introduction of modern methods of functional assessment into experimental and clinical projects significantly broadens knowledge of normal and pathological functioning of the visual system and is the basis for further development of new strategies of pathogenetic treatment, diagnostics and expert evaluation. Some problems of ophthalmology, including those that concern age-related macular degeneration, glaucoma, diabetic retinopathy, and other diseases, are considered in the context of how much electrophysiology contributes to their solution. The role of functional examinations of the retina in studying pathophysiology of neurodegenerative brain diseases, such as Alzheimer's and Parkinson's, is also discussed.

[Changes of retinal neurons and Muller glial cells in patients with type II diabetes in treatment of diabetic retinopathy with angiotensin-converting enzyme inhibitor].

Flicker-ERG (FERG) amplitude and glial indices Cg were measured to estimate angiotensin- converting enzyme (ACE) inhibitor Perindopril effect on retinal glial-neuronal interactions in patients with type II diabetes and diabetic retinopathy (DR). Intake of 5 mg Perindopril daily during 2 months improved photoreceptor and bipolar cells function in all stages of DR with the most significant effect in preproliferative DR (PPDR). After treatment course initially supernormal FERG scotopic glial indices reduced by 8,3-12 Hz (25-33%) in nonproliferative DR and PPDR and by 10% in proliferative DR. In photopic conditions moderate decrease of index was revealed in FERG by 30Hz only in PPDR. Obtained results show Perindopril to cause significant improvement of retinal glial-neuronal interactions in dark adaptation and poor positive dynamics in photopic conditions.

[Maturation and plasticity of visual system: neurogenesis, synaptogenesis, and myelogenesis. Report I. Retina and retinogeniculate projections].

In this review up-to-date conception of retinal neurogenesis and synaptogenesis is presented, specific stages information of cellular and synaptic structure of retinal synaptic pathways and their propable mechanisms are briefly discussed. Neurogenesis is largely determined geneticaly, and molecular cues are assumed to play a crucial role in retinal synaptogenesis. The initially established retinal synaptic circuitry is profoundly refined during postnatal development to form specific synaptic pathways. In early developing retina, retinal ganglion cells fire periodic bursts of action potentials that are highly correlated and propagate across the retina in a wave-like fashion. The model of retinal-wave-dependent synaptic plasticity seems to be suited for the Hebbian learning rule.

[Maturation and plasticity of visual system: neurogenesis, synaptogenesis, and myelogenesis. Report 2. Visual cortex and optic radiations].

Current conceptions of visual cortex synaptogenesis and mielination are reviewed. Human brain undergoes significant morphological and functional changes during prenatal period and the fist year of life that reflexes in height, latency and configuration of visual evoked potentials. The stages of neural modification are genetically predetermined, but it keeps developing under the influence of altered sensory experience. Period of accelerated development of nerve cells and formation of synaptic contacts is followed by global gradual elimination of exuberant neurons and their ineffective contacts, that promotes greater specificity of neuronal tissue and fine functional tuning. The importance of up-to-date functional and morphometric methods of brain maturation and plasticity research such as diffuse tractography is emphasized.

[Eye blood flow and its changes in patients with diabetes mellitus].

The main characteristics of retinal blood flow are presented including vessel diameter blood velocity, blood flow, perfusion pressure, indices of vasoresistance. The main methods of eye blood flow and retinal circulation examination are described. Comparative estimation of different techniques for eye haemodynamics examination in patients with diabetes mellitus is presented. The impact of autoregulation on blood flow changes is discussed.

[Nitrites can be reduced in retinal vessels during hypoxia and protect the retina against ischemia and apoptosis].

The possibility and the mechanism of the reduction of nitrites in retinal vessels under the acute hypoxia in vivo have been investigated. An experimental model of the rat retina ischemia was elaborated using the laser coagulation of retinal vessels. It was demonstrated that the vessel thrombosis does not occur if the nitrite concentration in the vessels is increased. It was proposed that, under acute hypoxia, nitrites are reduced to NO, which results in a drastic vasodilatation. Considering that the effect takes less than a minute, this reduction cannot be due to hypoxic acidosis but is more likely associated with NO reduction by heme proteins. It was found that the increased concentration of nitrites protects the retina from the development of ischemia progress and that the preliminary administration of nitrites prevents apoptosis in the retina and a decrease in its photoelectric activity.

[Molecular mechanisms of retinal ischemia].

The review discusses the molecular mechanisms of retinal damage, which are associated with retinal ischemia. Ischemia is one of the key factors determining the pathophysiology of many retinal diseases, such as diabetic retinopathy, glaucoma, anterior ischemic optic neuropathy, age-related macular degeneration, retinopathy of prematurity. Hypoxia and ischemia impair retinal neuronal energy metabolism, by launching a cascade of trigger reactions resulting in cell death. Oxidative stress, excitotoxicity, cell acidosis, inflammation, and others mechanisms acting in tandem are of considerable importance in ischemia. Neuronal apoptosis and neovascularization are the most important sequels of ischemia. Among all retinal neurons, ganglion cells are most susceptible to ischemia, which determines their early structural and functional changes in many ischemia-associated retinal diseases. The molecular mechanisms underlying the pathophysiology of ischemia-associated retinal diseases should be understood to substantiate and develop new therapy modalities.

[Electroretinography in the diagnosis and monitoring of treatment for neovascular age-related macular degeneration: Communication 1].

The pathophysiological mechanisms responsible for the development of choroidal neovascularization (CNV) in age-related macular degeneration (ARMD) still remain to be little studied and clinical electrophysiology that has a wide spectrum of objective studies plays a great role in the assessment of regularities of retinal functional changes in this disease. Recording of different types of electroretinograms (ERG) from the ISCEV standards and multifocal ERG is most extensively used to characterize CNV. The review considers the pattern of ERG changes in normal physiological aging and the specific features of suppressed retinal electrogenesis in neovascular ARMD. The diagnostic capacities of different electroretinographic methods, their disadvantages and limits in the evaluation of retinal functions in patients with CNV are compared.

[Electroretinography in the diagnosis and monitoring of treatment for neovascular age-related macular degeneration: Communication 2].

Electroretinography is an informative tool in evaluating retinal function in age-related macular degeneration (ARMD) and in monitoring the treatment of choroidal neovascularization (CNV). The review gives the results of electroretinographic studies in the monitoring of CNV, by using photodynamic therapy (PDT) and angiostatic agents and in combined PDT and anti-VEGF therapy. The regularities of retinal functional changes in the early and late periods after mono- and combined therapy are considered. The informative value of various electroretinographic studies was compared in the evaluation of retinal functional changes after therapy and in the prediction of its efficiency. Multifocal electroretinography is today of the greatest value among other conventional methods; however, there is a need for searching for new objective indicators that enable assessment of progress in the treatment of neovascular ARMD and optimization of indications for this or that treatment, particularly when new and expensive technologies of treating CNV emerge.

[Electroretinography in regmatogenic retinal detachment in the myopic eye].

The investigation studied the topographic features of retinal electrogenesis in regmatogenic retinal detachment (RRD) in the myopic eye, by using multifocal electroretinography (mfERG). Both eyes from 12 patients were used to analyze the amplitude and latency of the first negative and positive mfERG first-order kernel components averaged over the entire stimulation area, by rings, quadrants of vision fields and in the areas of the adjacent and detached retina. The myopic eye in RRD even without macular involvement showed a selective reduction in R1 amplitude when central retinal rings 1 and 2 were stimulated, which suggests that the macular region is highly sensitive to the impaired anatomic integrity of the adjoining retinal zones. Longer latency of mfERG N1 is most typical of the stimulation of the retinal macular region in recent RRD, and that is characteristic of the near and middle retinal periphery in a 1-2-month history of RRD, which may be indicative of the progression of impairments in the rod system. The reduction in P1 amplitude is most pronounced in a 1-2-month history of RRD. The findings suggest that a 1-month history is critical in the development of specific functional changes in the detached retina and mainly in its mid-periphery and support a need for early (less than 4-week) surgical treatment for retinal detachment particularly in the eyes of patients with myopic changes in the eye grounds. The authors show it advisable to widely use a preliminary test protocol in poor unilateral gaze fixation (19 hexagons), which causes an increase in recording purity and, therefore, promotes the reliability of the findings.

Experimental model of acute ischemia of the retina in rats.

We studied the development of retinal ischemia in rat eye after laser coagulation of blood vessels. Typical signs of ischemia manifested in the retina after 24 h: development of stable retinal edema, decrease in the b/a index (ratio of the electroretinogram b and a-wave amplitudes) to 1-2 units, pronounced disorders in the retinal microcirculation system, leading to ischemia of the inner layers of the retina. The proposed model is convenient for studies of the development of acute retinal ischemia, is easily realized, and reproduces some acute ischemic diseases of the retina.

[A model of retinal ischemia: clinicofunctional and histological studies].

A new procedure is proposed for the experimental simulation of retinal ischemia, which develops the latter of the preset area and depth. The clinical and morphofunctional characteristics of retinal ischemia are given. Simulation of retinal ischemia via the photocoagulation effect of argon laser on the rabbit great retinal vessels demonstrated an inflammatory reaction, followed by occlusion and the development of ischemia in the blood-supplied retinal layers, vascular endothelial damage at the site of laser coagulation. There was a persistent (as long as 3 weeks) impairment in retinal electrogenesis with two-phase changes in the amplitude of a- and b-waves on an electroretinogram and in the hypoxia index b/a. Histological studies showed that evolving ischemia afflicted the internal retinal layers, primarily involving the layer ofganglionic cells and nerve fibers, which was also attended by a significant reduction in the level of venous outflow and, thus, it was of mixed (arteriovenous) nature.