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.
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 Animals with spontaneous tumors have largely been replaced by engrafted and genetically engineered models.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.
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: Spontaneously resolved primary congenital glaucoma is rare and the mechanism remains unknown. Previous literature described the phenomenon of spontaneous resolution of primary congenital glaucoma, with no further reports on follow-up visits and visual development of patients. We report a case of unilateral spontaneously resolved primary congenital glaucoma at a 7-year follow-up visit and describe the differential development of axial length (AL) between affected eye and healthy eye.
Case Description: A 6-year-old boy firstly presented at Zhongshan Ophthalmic Center with expanded corneas and ruptures in Descemet’s membranes (Haab’s striae) and apparently thin retinal nerve fiber layer (RNFL) in the left eye (LE), but normal intraocular pressure (IOP) of both eyes without anti-glaucoma medications or surgeries. At 7-year follow-up, the IOPs of bilateral eyes were stable ranging from 8 to 11 mmHg. A cup to disc ratio and the RNFL was stable in the LE at the following visit. The AL increased almost 3 mm in the right eye (RE) but 1.5 mm in the LE. Without anti-glaucoma medications or surgeries, the primary congenital glaucoma was spontaneously resolved.
Conclusions: It may figure out the development and influence of the affected eye of the patient, including AL and refraction state with regular ophthalmic examination at periodic follow-up.
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 and Objective: Subthreshold laser therapy has emerged as a therapeutic alternative to traditional laser photocoagulation for certain ophthalmic diseases including central serous chorioretinopathy (CSCR), diabetic macular edema (DME), macular edema secondary to branch retinal vein occlusion (BRVO), and age-related macular degeneration (AMD). The objective of this paper is to review and discuss the clinical applications of subthreshold laser and the mechanisms of different subthreshold laser techniques including subthreshold micropulse laser (SMPL), selective retina therapy (SRT), subthreshold nanosecond laser (SNL), endpoint management (EpM), and transpupillary thermotherapy (TTT).
Methods: A narrative review of English literature and publicly available information published before November 2021 from literature databases and computerized texts. We discuss the currently available subthreshold laser systems and the advancements made to perform different subthreshold laser techniques for various ophthalmic diseases. We highlight various clinical studies and therapeutic techniques that have been conducted to further understand the effectiveness of subthreshold laser in the clinical setting. We conclude the article by covering emerging subthreshold laser systems that are currently being developed for future clinical use. The PubMed database was utilized for peer-reviewed articles and pertinent information on subthreshold systems was cited from publicly available online websites covering specific systems.
Key Content and Findings: Various subthreshold laser systems have been developed to treat certain retinal diseases. Several systems are currently in development for future clinical applications.
Conclusions: While conventional laser photocoagulation has been effective in treating various retinal diseases, subthreshold laser systems aim to provide a therapeutic effect without visible signs of damage to the underlying tissue. This technology may be particularly effective in treating macular disorders. Further clinical studies are needed to evaluate their role in the management of retinal diseases.
