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.
Abstract: Submacular haemorrhage (SMH) is a sight threatening complication that can occur in exudative age related macular degeneration (AMD), but has been described to occur more frequently in eyes with polypoidal choroidal vasculopathy (PCV). Left untreated, SMH carries a grave visual prognosis. Thus, expedient diagnosis and effective management of this complication is of paramount importance. The treatment strategies for SMH include (I) displacement of blood from the fovea, usually by injection of an expansile gas; (II) pharmacologic clot lysis such as with recombinant tissue plasminogen activator (rtPA); and (III) treatment of the underlying choroidal neovascularization (CNV) or PCV, such as with anti-vascular endothelial growth factor (anti-VEGF) agents. These three strategies have been employed in isolation or in combination, some concurrently and others in stages. rtPA has demonstrable effect on the liquefaction of submacular clots but there are remaining uncertainties with regards to the dose, safety and the timing of initial and repeat treatments. Potential side effects of rtPA include retinal pigment epithelial toxicity, increased risk of breakthrough vitreous haemorrhage and systemic toxicity. In cases presenting early, pneumatic displacement alone with anti-VEGF may be sufficient. Anti-VEGF monotherapy is a viable treatment option particularly in patients with thinner SMH and those who are unable to posture post pneumatic displacement.
Background: The ex vivo model represented by mouse retinal explants in culture is a useful experimental model to investigate the molecular mechanism involved in neurovascular diseases such as diabetic retinopathy (DR). It ensures an experimental overview with more complete respect to isolate cells and reduce problems in terms of accessibility and management with respect to in vivo model. In particular, it allows the evaluation of the relationship between retinal cells in response to the typical stressors involved in DR pathogenesis.
Methods: Ex vivo retinal fragments derived from 3- to 5-week-old C57BL/6J mice. In particular, after dissection, the retina is cut into 4 separate fragments and transferred onto inserts placed with ganglion cells up. Once in culture, the explants could be treated in stress conditions typical of DR. In particular, this study protocol describes the procedure for the preparation and the culture of retinal explants with specific metabolic stressors such as high glucose (HG), advanced glycation end product (AGE), and oxidative stress (OS). In the end, this paper provides the protocols to perform molecular analyses in order to evaluate the response of retinal explants to stress and/or neuroprotective treatments.
Discussion: The cultured retinal explants represent an ex vivo experimental model to investigate the molecular mechanisms involved in neurovascular diseases such as DR. Moreover, they could be useful to test the effect of neuroprotective compounds in response to metabolic stressors in a fewer time respect to an in vivo model. In conclusion, retinal explants in culture represent a valuable experimental model to conduct further studies to better understand the pathophysiology of DR.
Background: Retinal degeneration is a common feature of several retinal diseases, such as retinitis pigmentosa and age-related macular degeneration (AMD). In this respect, experimental models of photo-oxidative damage reproduce faithfully photoreceptor loss and many pathophysiological events involved in the activation of retinal cell degeneration. Therefore, such models represent a useful tool to study the mechanisms related to cell death. Their advantage consists in the possibility of modulating the severity of damage according to the needs of the experimenter. Indeed, bright light exposure could be regulated in both time and intensity to trigger a burst of apoptosis in photoreceptors, allowing the study of degenerative mechanisms in a controlled fashion, compared to the progressive and slower rate of death in other genetic models of photoreceptor degeneration.
Methods: Here, an exemplificative protocol of bright light exposure in albino rat is described, as well as the main outcomes in retinal function, photoreceptor death, oxidative stress, and inflammation, which characterize this model and reproduce the main features of retinal degeneration diseases.
Discussion: Models of photo-oxidative damage represent a useful tool to study the mechanisms responsible for photoreceptor degeneration. In this respect, it is important to adapt the exposure paradigm to the experimental needs, and the wide range of variables and limitations influencing the final outcomes should be considered to achieve proper results.
Trial Registration: None.
Background: Retinopathy of prematurity (ROP) is considered as the most common reason for blindness in children, particularly in preterm infants. The disease is characterized by the dysregulation of angiogenic mechanisms due to preterm birth, leading ultimately to vascular abnormalities and pathological neovascularization (NV). Retinal detachment and vision loss could represent a concrete risk connected to the most severe forms of ROP, also characterized by inflammation and retinal cell death.
Methods: During the last decades, many animal models of oxygen-induced retinopathy (OIR) have been recognized as useful tools to study the mechanisms of disease, since they reproduce the hallmarks typical of human ROP. Indeed, modulation of retinal vascular development by exposure to different oxygen protocols is possible in these animals, reproducing the main pathological phenotypes of the disease. The easy quantification of abnormal NV and the possibility to perform electrophysiologic, histological and molecular analyses on these models, make OIR animals a fundamental instrument in studying the pathophysiology of ROP and the effects of novel treatments against the disease.
Discussion: Here, the most commonly used OIR protocols in rodents, such as mice and rats, are described as well as the main pathological outcomes typical of these models. Despite their limitations and variables which should be considered whilst using these models, OIR models display several characteristics which have also been confirmed in human patients, validating the usefulness of such animals in the pre-clinical research of ROP.
