Background: For years, studies using several animal models have highlighted the predominant role of the primary visual area in visual information processing. Its six cortical layers have morphological, hodological and physiological differences, although their roles regarding the integration of visual contrast and the messages sent by the layers to other brain regions have been poorly explored. Given that cortical layers have distinct properties, this study aims to understand these differences and how they are affected by a changing visual contrast.
Methods: A linear multi-channel electrode was placed in the primary visual cortex (V1) of the anesthetized mouse to record neuronal activity across the different cortical layers. The laminar position of the electrode was verified in real time by measuring the current source density (CSD) and the multi-unit activity (MUA), and confirmed post-mortem by histological analysis. Drifting gratings varying in contrast enabled the measurement of the firing rate of neurons throughout layers. We fitted this data to the Naka-Rushton equations, which generated the contrast response function (CRF) of neurons.
Results: The analysis revealed that the baseline activity as well as the rate of change of neural discharges (the slope of the CRF) had a positive correlation across the cortical layers. In addition, we found a trend between the cortical position and the contrast evoking the semi-saturation of the activity. A significant difference in the maximum discharge rate was also found between layers II/III and IV, as well as between layers II/III and V.
Conclusions: Since layers II/III and V process visual contrast differently, our results suggest that higher cortical visual areas, as well subcortical regions, receive different information regarding a change in visual contrast. Thus, a contrast may be processed differently throughout the different areas of the visual cortex.
Abstract: Contrast is the differential luminance between one object and another. Contrast sensitivity (CS) quantifies the ability to detect this difference: estimating contrast threshold provides information about the quality of vision and helps diagnose and monitor eye diseases. High contrast visual acuity assessment is traditionally performed in the eye care practice, whereas the estimate of the discrimination of low contrast targets, an important complementary task for the perception of details, is far less employed. An example is driving when the contrast between vehicles, obstacles, pedestrians, and the background is reduced by fog. Many conditions can selectively degrade CS, while visual acuity remains intact. In addition to spatial CS, “temporal” CS is defined as the ability to discriminate luminance differences in the temporal domain, i.e., to discriminate information that reaches the visual cortex as a function of time. Likewise, temporal sensitivity of the visual system can be investigated in terms of critical fusion frequency (CFF), an indicator of the integrity of the magnocellular system that is responsible for the perception of transient stimulations. As a matter of fact, temporal resolution can be abnormal in neuro-ophthalmological clinical conditions. This paper aims at considering CS and its application to the clinical practice.
Abstract: Optical coherence tomography (OCT) is a technology that is widely used to assess structural abnormalities in the retina for a variety of pediatric conditions. The introduction of this instrument has allowed for widespread access to minimally invasive standardized, reproducible quantified structural assessments of the optic nerve and retina. This has had important implications in pediatric optic neuropathies, populations in whom monitoring of disease activity is essential to making treatment decisions. OCT has had particular relevance for inflammatory optic neuropathies, as onset of an inflammatory optic neuropathy may herald the onset of a chronic inflammatory disorder of the central nervous system (CNS) such as multiple sclerosis, neuromyelitis optica spectrum disorder (aquaporin 4 antibody positive), and myelin oligodendrocyte glycoprotein (MOG) associated disorders. This paper will focus on the application of OCT technology to this group of disorders in pediatrics. After reviewing pediatric-specific anatomic and practical issues pertinent to OCT, we will review knowledge related to the use of OCT in inflammatory pediatric optic neuropathies, with a focus on structural outcomes and their correlation with functional outcome metrics.
Abstract: Optical coherence tomography (OCT) provides a non-invasive analysis of the retina in vivo. Lesions which compress the anterior visual pathway can cause anterograde and retrograde neuro-degeneration. Retrograde structural changes to the retina can be detected by OCT. Analyzing patterns of change on OCT can guide diagnostic and treatment decisions for lesions compressing the optic nerve and chiasm to minimize loss of visual function. From our review of current literature, it is clear that thinning of both the retinal nerve fiber and ganglion cell layers (GCLs) can indicate compression. These parameters correlate with visual function loss as detected by perimetry. Furthermore, these measurements have shown to be the most reliable biomarkers to date in predicting visual recovery after treatment of these compressive lesions.
Perception is the ability to see, hear, or become aware of external stimuli through the senses. Visual stimuli are electromagnetic waves that interact with the eye and elicit a sensation. Sensations, indeed, imply the detection, resolution, and recognition of objects and images, and their accuracy depends on the integrity of the visual system. In clinical practice, evaluating the integrity of the visual system relies greatly on the assessment of visual acuity, that is to say on the capacity to identify a signal. Visual acuity, indeed, is of utmost importance for diagnosing and monitoring ophthalmological diseases. Visual acuity is a function that detects the presence of a stimulation (a signal) and resolves its detail(s). This is the case of a symbol like “E”: the stimulus is detected, then it is resolved as three horizontal bars and a vertical bar. In fact, within the clinical setting visual acuity is usually measured with alphanumeric symbols and is a three-step process that involves not only detection and resolution, but, due to the semantic content of letters and numbers, their recognition. Along with subjective (psychophysical) procedures, objective methods that do not require the active participation of the observer have been proposed to estimate visual acuity in non-collaborating subjects, malingerers, or toddlers. This paper aims to explain the psychophysical rationale underlying the measurement of visual acuity and revise the most common procedures used for its assessment.
Abstract: In the early days of deciphering the injured neuronal tissues led to the realization that contrast is necessary to discern the parts of the recovering tissues from the damaged ones. Early attempts relied on available (and often naturally occurring) staining substances. Incidentally, the active ingredients of most of them were small molecules. With the advent of time, the knowledge of chemistry helped identify compounds and conditions for staining. The staining reagents were even found to enhance the visibility of the organelles. Silver impregnation identification of Golgi bodies was discovered in owl optic nerve. Staining reagents since the late 1800s were widely used across all disciplines and for nerve tissue and became a key contributor to advancement in nerve-related research. The use of these reagents provided insight into the organization of the neuronal tissues and helped distinguish nerve degeneration from regeneration. The neuronal staining reagents have played a fundamental role in the clinical research facilitating the identification of biological mechanisms underlying eye and neuropsychiatric diseases. We found a lack of systematic description of all staining reagents, whether they had been used historically or currently used. There is a lack of readily available information for optimal staining of different neuronal tissues for a given purpose. We present here a grouping of the reagents based on their target location: (I) the central nervous system (CNS), (II) the peripheral nervous system (PNS), or (III) both. The biochemical reactions of most of the staining reagents is based on acidic or basic pH and specific reaction partners such as organelle or biomolecules that exists within the given tissue type. We present here a summary of the chemical composition, optimal staining condition, use for given neuronal tissue and, where possible, historic usage. Several biomolecules such as lipids and metabolites lack specific antibodies. Despite being non-specific the reagents enhance contrast and provide corroboration about the microenvironment. In future, these reagents in combination with emerging techniques such as imaging mass spectrometry and kinetic histochemistry will validate or expand our understanding of localization of molecules within tissues or cells that are important for ophthalmology and vision science.
Background: Axonal degeneration caused by damage to the optic nerve can result in a gradual death of retinal ganglion cells (RGC), leading to irreversible vision loss. An example of such diseases in humans includes optic nerve degeneration in glaucoma. Glaucoma is characterized by the progressive degeneration of the optic nerve and the loss of RGCs that can lead to loss of vision. The different animal models developed to mimic glaucomatous neurodegeneration, all result in RGC loss consequent optic nerve damage.
Methods: The present article summarizes experimental procedures and analytical methodologies related to one experimental model of glaucoma induced by optic nerve crush (ONC). Point-by-point protocol is reported with a particular focus on the critical point for the realization of the model. Moreover, information on the electroretinogram procedure and the immunohistochemical detection of RGCs are described to evaluate the morpho-functional consequences of ONC.
Discussion: Although the model of ONC is improperly assimilated to glaucoma, then the ONC model simulates most of the signaling responses consequent to RGC apoptosis as observed in models of experimental glaucoma. In this respect, the ONC model may be essential to elucidate the cellular and molecular mechanisms of glaucomatous diseases and may help to develop novel neuroprotective therapies.
Background: The complexity of the glaucoma pathophysiology is directly reflected on its experimental modeling for studies about pathological mechanisms and treatment approaches. Currently, a variety of in vivo models are available for the study of glaucoma, although they do not reach an exact reproduction of all aspects characterizing the human glaucoma. Therefore, a comprehensive view of disease onset, progression and treatment efficacy can only be obtained by the integration of outcomes deriving from different experimental models.
Methods: The present article summary experimental procedures and analytical methodologies related with two experimental models of glaucoma belonging to the classes of induced intraocular pressure (IOP)-elevation and genetic models, methyl cellulose (MCE)-induced ocular hypertension and DBA/2J mouse strain. Point-by-point protocols are reported with a particular focus on the critical point for the realization of each model. Moreover, typical strength and drawbacks of each model are described in order to critically handle the outcomes deriving from each model.
Discussion: This paper provides a guideline for the realization, analysis and expected outcomes of two models allowing to study IOP-driven neurodegenerative mechanisms rather than IOP-independent neurodegeneration. The complementary information from these models could enhance the analysis of glaucomatous phenomena from different points of view potentiating the basic and translational study of glaucoma.
Background: The complexity of the glaucoma pathophysiology is directly reflected on its experimental modeling for studies about pathological mechanisms and treatment approaches. Currently, a variety of in vivo models are available for the study of glaucoma, although they do not reach an exact reproduction of all aspects characterizing the human glaucoma. Therefore, a comprehensive view of disease onset, progression and treatment efficacy can only be obtained by the integration of outcomes deriving from different experimental models.
Methods: The present article summary experimental procedures and analytical methodologies related with two experimental models of glaucoma belonging to the classes of induced intraocular pressure (IOP)-elevation and genetic models, methyl cellulose (MCE)-induced ocular hypertension and DBA/2J mouse strain. Point-by-point protocols are reported with a particular focus on the critical point for the realization of each model. Moreover, typical strength and drawbacks of each model are described in order to critically handle the outcomes deriving from each model.
Discussion: This paper provides a guideline for the realization, analysis and expected outcomes of two models allowing to study IOP-driven neurodegenerative mechanisms rather than IOP-independent neurodegeneration. The complementary information from these models could enhance the analysis of glaucomatous phenomena from different points of view potentiating the basic and translational study of glaucoma.
