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 Animals with spontaneous tumors have largely been replaced by engrafted and genetically engineered models.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: Dry eye disease is the most prevalent ocular surface disease in eye clinics. The deficiency of tears is regarded as one of the main pathogenic factors for this disease. Due to the fact that the components of tears are still far beyond our knowledge, the restoration of physiological tears remains the optimum choice for dry eye patients. However, the traditional way to stimulate tear production by systemic administration of muscarinic agonists usually encounters severe side effects. Recently, Nakamachi and colleagues reported that PACAP, a native neurotransmitter present in tear fluid, could stimulate main lacrimal gland secretion and relieve dry eye-like symptoms in PACAP knockout mice. The finding of PACAP and its underlying mechanisms suggest a new modality for dry eye treatment via targeted topical tear stimulations.
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.
