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.
Background and Objective: Intraocular lymphoma (IOL) is a heterogenous category of rare malignancies that are often misdiagnosed and underrecognized. The rarity of IOL impedes clinical research and contributes to difficulty in standardizing its management. In this article we review the existing scientific literature to identify the current diagnostic tools and discuss comprehensive management of various categories of IOL. Our objective is to increase disease recognition of IOL as a whole and explore updated management options for each subtype.
Methods: PubMed and Embase were searched for publications using the terms ‘intraocular lymphoma’, ‘vitreoretinal lymphoma’, ‘uveal lymphoma’, ‘iris lymphoma’, ‘choroidal lymphoma’ and ‘ciliary body lymphoma’ published from 1990 to June 2021. Inclusion criteria were English language articles. Exclusion criteria were non-English language articles, case reports and animal studies.
Key Content and Findings: IOL often presents in middle-aged and older patients with symptoms of floaters and vision changes, but a broad array of clinical signs and symptoms are possible depending upon subtype. IOL can be subdivided by location of involvement into vitreoretinal and uveal lymphoma. These subtypes express key differences in their pathophysiology, clinical presentation, histology, prognosis, and treatment. Primary vitreoretinal lymphomas (PVRL) generally originate from B-lymphocytes and are associated with central nervous system (CNS) lymphoma. Ophthalmic findings include retinal pigment epithelium changes with yellow subretinal deposits known as “leopard spotting.” Primary uveal lymphomas generally originate from low-grade B-lymphocytes invading the choroid and carry an improved prognosis compared to vitreoretinal lymphomas. Funduscopic findings of primary uveal lymphoma include yellow to pink-yellow choroidal swelling with infiltrative subconjunctival “salmon-patch” lesions. Diagnosis for IOL is often delayed due to insidious onset, low prevalence, and tendency to mimic diseases such as uveitis. Diagnosis may be challenging, often relying on biopsy with specialized laboratory testing for confirmation of IOL. Optimal treatment regimens are currently debated among experts. Management of IOL is best coordinated in association with neuro-oncology clinicians due to the tendency for intracranial involvement.
Conclusions: IOL represents a group of multiple malignancies with distinct clinicopathologic features. Future outlook for treatment and prognosis of IOL is likely to improve with less invasive molecular diagnostic techniques and increased awareness. Clinicians should be circumspect in all patients with possible IOL and promptly refer to oncologic specialists for rapid evaluation and treatment.
Background and Objective: Subthreshold laser technologies and their applications in ophthalmology have greatly expanded in the past few decades. Initially used for retinal diseases such as central serous chorioretinopathy and diabetic macular edema, subthreshold lasers have recently shown efficacy in the treatment of various types of glaucoma. Our primary objectives are to review the clinical applications of subthreshold laser in the context of glaucoma treatment and discuss the mechanisms of different subthreshold laser techniques, including subthreshold selective laser trabeculoplasty (SSLT), micropulse laser trabeculoplasty (MLT), pattern-scanning laser trabeculoplasty (PSLT), titanium laser trabeculoplasty (TLT), and micropulse transscleral cyclophotocoagulation (MP-TSCPC).
Methods: This was a narrative review compiled from literature of PubMed and Google Scholar. The review was performed from March 2021 to October 2021 and included publications in English. We also included information from web pages to cover details of relevant laser systems. We discuss the history of subthreshold laser, recent advancements in subthreshold techniques, and commercially available systems that provide subthreshold capabilities for glaucoma. We highlight basic science and clinical studies that deepen the understanding of treatment mechanisms and treatment effectiveness in the clinical setting respectively. We review commonly used parameters for each technique and provide comparisons to conventional treatments.
Key Content and Findings: We found five distinct types of subthreshold laser used in the management of glaucoma. Numerous subthreshold laser systems are commercially available and can provide this treatment. Therefore, understanding the differences between subthreshold techniques and laser systems will be critical in utilizing subthreshold laser in the clinical setting.
Conclusions: Traditional laser trabeculoplasty (LT) and cyclophotocoagulation (CPC) have shown effectiveness in the treatment of various types of glaucoma but are associated with visible damage to the underlying tissue and adverse effects. Subthreshold laser systems aim to provide the therapeutic effect found in traditional lasers, while minimizing unwanted treatment related effects. Further clinical studies are needed to evaluate the role of subthreshold lasers in the management of glaucoma.
