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.

Backgrounds: To assess changes in anterior segment biometry during accommodation using a swept source anterior segment optical coherence tomography (SS-OCT). Methods: One hundred-forty participants were consecutively recruited in the current study. Each participant underwent SS-OCT scanning at 0 and -3 diopter (D) accommodative stress after refractive compensation, and ocular parameters including anterior chamber depth (ACD), anterior and posterior lens curvature, lens thickness (LT) and lens diameter were recorded. Anterior segment length (ASL) was defined as ACD plus LT. Lens central point (LCP) was defined as ACD plus half of the LT. The accommodative response was calculated as changes in total optical power during accommodation. Results: Compared to non-accommodative status, ACD (2.952±0.402 vs. 2.904±0.382 mm, P<0.001), anterior (10.771±1.801 vs. 10.086±1.571 mm, P<0.001) and posterior lens curvature (5.894±0.435 vs. 5.767±0.420 mm, P<0.001), lens diameter (9.829±0.338 vs. 9.695±0.358 mm, P<0.001) and LCP (4.925±0.274 vs. 4.900±0.259 mm, P=0.010) tended to decreased and LT thickened (9.829±0.338 vs. 9.695±0.358 mm, P<0.001), while ASL (6.903±0.279 vs. 6.898±0.268 mm, P=0.568) did not change significantly during accommodation. Younger age (β=0.029, 95% CI: 0.020 to 0.038, P<0.001) and larger anterior lens curvature (β=-0.071, 95% CI: -0.138 to -0.003, P=0.040) were associated with accommodation induced greater steeping amplitude of anterior lens curvature. The optical eye power at 0 and -3 D accommodative stress was 62.486±2.284 and 63.274±2.290 D, respectively (P<0.001). Age was an independent factor of accommodative response (β=-0.027, 95% CI: -0.038 to -0.016, P<0.001). Conclusions: During -3 D accommodative stress, the anterior and posterior lens curvature steepened, followed by thickened LT, fronted LCP and shallowed ACD. The accommodative response of -3 D stimulus is age-dependent.

Abstract: Red eye is common in our daily practice. It ranges from non-inflammatory to inflammatory causes. An extended course of disease should prompt suspicion and the possibility of diagnosis revision. A prolonged conjunctivitis mimicking nodular episcleritis can be presented as a manifestation of granulomatosis with polyangiitis (GPA). A 57-year-old woman complained of eye redness and tearing for two weeks which partially resolved with antibiotics. She was subsequently commenced on topical and oral non-steroidal anti-inflammatory drugs (NSAIDs) and topical anti-allergic. However, in the following reviews she developed cornea thinning and her systemic examination revealed an injected uvula with absence of upper respiratory tract infection. She was investigated for connective tissue disease and found to have raised anti-inflammatory markers and her antinuclear antibody and C-ANCA tests were positive. She was diagnosed with GPA. Her conditions improved followed by the commencement of topical corticosteroid with high dose of systemic corticosteroid, which followed by a tapering regime with oral corticosteroid. Although red eye is common, it is associated with a variety of diseases. GPA manifestation can be as subtle as a red eye. Any prolonged partially treated red eye should prompt suspicion of a more sinister cause. Sensitive detection of other subtle systemic signs is very important.

Objective: In this review, non-transgenic models of age-related macular degeneration (AMD) are discussed, with focuses on murine retinal degeneration induced by sodium iodate and lipid peroxide (HpODE) as preclinical study platforms.

Background: AMD is the most common cause of vision loss in a world with an increasingly aging population. The major phenotypes of early and intermediate AMD are increased drusen and autofluorescence, Müller glia activation, infiltrated subretinal microglia and inward moving retinal pigment epithelium (RPE) cells. Intermediate AMD may progress to advanced AMD, characterized by geography atrophy and/or choroidal neovascularization (CNV). Various transgenic and non-transgenic animal models related to retinal degeneration have been generated to investigate AMD pathogenesis and pathobiology, and have been widely used as potential therapeutic evaluation platforms.

Methods: Two retinal degeneration murine models induced by sodium iodate and HpODE are described. Distinct pathological features and procedures of these two models are compared. In addition, practical protocol and material preparation and assessment methods are elaborated.

Conclusions: Retina degeneration induced by sodium iodate and HpODE in mouse eye resembles many clinical aspects of human AMD and complimentary to the existent other animal models. However, standardization of procedure and assessment protocols is needed for preclinical studies. Further studies of HpODE on different routes, doses and species will be valuable for the future extensive use. Despite many merits of murine studies, differences between murine and human should be always considered.

Background: Continuous and primary in vitro cultures are largely used to study cellular mechanisms occurring in several pathologic-like or pathological conditions. Continuous cell lines allow to perform long-lasting experiments since they do not undergo senescence.

Methods: The immortalized Moorfields/Institute of Ophtalmology-Müller 1 (MIO-M1) cell type represents a valuable model to analyze the mechanistic pathways characterizing Müller glial cells, both in health and in disease. MIO-M1 can be used to dissect the response of these glial cells following treatments which mimic pathological condition. For instance, MIO-M1 are useful to study the response of this cell type to stress condition as the case of oxidative stress (OS) (cultured with hydrogen peroxide), pathological neovascularization (cultured with VEGF), hypoxic or hyperoxic condition (cultured in low or high oxygen chamber). On the other hand, primary cultures allow to specifically analyze cellular responses without the interference of the whole organ, although the experimental treatment is performed in vivo. Primary Müller cells can be used to perform electrophysiological analyses of different cell sites.

Discussion: We describe how to manage MIO-M1 cells and how to analyze their response to different stress conditions; moreover, we report how to isolate and identify primary Müller cells and how to perform patch clamp and single cell recordings on them.

Abstract: Animal models are crucial for the study of tumorigenesis and therapies in oncology research. Though rare, uveal melanoma (UM) is the most common intraocular tumor and remains one of the most lethal cancers. Given the limitations of studying human UM cells in vitro, animal models have emerged as excellent platforms to investigate disease onset, progression, and metastasis. Since Greene’s initial studies on hamster UM, researchers have dramatically improved the array of animal models. Animals with spontaneous tumors have largely been replaced by engrafted and genetically engineered models. Inoculation techniques continue to be refined and expanded. Newer methods for directed mutagenesis have formed transgenic models to reliably study primary tumorigenesis. Human UM cell lines have been used to generate rapidly growing xenografts. Most recently, patient-derived xenografts have emerged as models that closely mimic the behavior of human UM. Separate animal models to study metastatic UM have also been established. Despite the advancements, the prognosis has only recently improved for UM patients, especially in patients with metastases. There is a need to identify and evaluate new preclinical models. To accomplish this goal, it is important to understand the origin, methods, advantages, and disadvantages of current animal models. In this review, the authors present current and historic animal models for the experimental study of UM. The strengths and shortcomings of each model are discussed and potential future directions are explored.

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: In this investigation, we explore the literature regarding neuroregeneration from the 1700s to the present. The regeneration of central nervous system neurons or the regeneration of axons from cell bodies and their reconnection with other neurons remains a major hurdle. Injuries relating to war and accidents attracted medical professionals throughout early history to regenerate and reconnect nerves. Early literature till 1990 lacked specific molecular details and is likely provide some clues to conditions that promoted neuron and/or axon regeneration. This is an avenue for the application of natural language processing (NLP) to gain actionable intelligence. Post 1990 period saw an explosion of all molecular details. With the advent of genomic, transcriptomics, proteomics, and other omics—there is an emergence of big data sets and is another rich area for application of NLP. How the neuron and/or axon regeneration related keywords have changed over the years is a first step towards this endeavor.

Methods: Specifically, this article curates over 600 published works in the field of neuroregeneration. We then apply a dynamic topic modeling algorithm based on the Latent Dirichlet allocation (LDA) algorithm to assess how topics cluster based on topics.

Results: Based on how documents are assigned to topics, we then build a recommendation engine to assist researchers to access domain-specific literature based on how their search text matches to recommended document topics. The interface further includes interactive topic visualizations for researchers to understand how topics grow closer and further apart, and how intra-topic composition changes over time.

Conclusions: We present a recommendation engine and interactive interface that enables dynamic topic modeling for neuronal regeneration.

Background: Sodium iodate (SI) is a chemical widely applied to induce retina degeneration in animal models. SI treatment caused formation of rosettes/folds in the outer nuclear layer (ONL) of the rat retina, but it was previously unclear whether SI also forms rosettes in mice. In addition, SI induced retina degeneration was never addressed in non-separate sclerochoroid/retina pigment epithelium/retina whole mount. Here we displayed features of retina degeneration including rosette formation in mice and developed a morphological analytic assessment using sclerochoroid/retina pigment epithelium/retina whole mounts.

Methods: SI was intraperitoneally injected in Sprague-Dawley (SD) rats and C57BL/6J mice using a single dose (50 mg/kg) or with a dose range (10 to 50 mg/kg) in BALB/C mice. Rat retinas were investigated up to 2-week post-injection by histology and whole mounts, and mouse retinas were investigated up to 3-week post-injection by histology, fluorescent staining of sections and/or sclerochoroid/retina pigment epithelium/retina whole mounts for the morphological evaluations of the SI-induced retina damage.

Results: SI-induced retina damage caused photoreceptor (PR) degeneration and rosettes/folds formation, as well as retina pigment epithelium degeneration and inward migration. It displayed mixed nuclei from choroid to PRs, due to layer disorganization, as shown by single horizontal images in the sclerochoroid/retina pigment epithelium/retina whole mounts. Measurement of the PR rosette area induced by SI provided a quantitative, morphological evaluation of retina degeneration.

Conclusions: The method of non-separate sclerochoroid/retina pigment epithelium/retina whole staining and mount allows us to observe the integral horizontal view of damage from sclera to PR layers, which cannot be addressed by using sectioned and separate whole mount methods. This method is applicable for morphological evaluation of retina damage, especially in the subretinal layer.