Abstract: Age-related macular degeneration (ARMD), one of the most common causes of blindness, should be considered more due to its exponential increase in the coming 20 years as a result of increasing the age of the population. Whereas more recent studies offered newer scaling systems for ARMD, traditionally it is classified as the early and late stages. The main injury in this disease occurred in retinal pigment epithelium (RPE) and the retina. RPE cells have a crucial role in hemostasis and supporting photoreceptors. In the early stages, damages to RPE are minimal and mainly no treatment is needed because most patients are asymptomatic. However, in the late stages, RPE impairment may lead to the invasion of choroidal vessels into the retina. Although anti-angiogenic agents can inhibit this abnormal growth of blood vessels, they cannot stop it completely, and finally, total loss of retinal cells may occur (geographical atrophy). Since this prevalent disease has not had any cure yet, the concept of substituting the RPE cells should be considered. Repairing the injury to central nervous system cells is almost impossible because the regenerative capacity of these cells is limited. Recently, the use of regenerative substitutes has been suggested to replace damaged tissues. Amniotic membrane (AM) has been raised as a suitable substitute for damaged RPE cells due to all of its unique properties: pluripotency, anti-angiogenic effect, and anti-inflammatory effect. Based on the few studies that have been published so far, it seems that the use of this membrane in the treatment of ARMD can be helpful, but more studies are needed.
Abstract: Statins are used widely to treat hypercholesterolemia and atherosclerotic cardiovascular disease. They have inflammatory and immunomodulatory effects potentially useful for managing systemic autoimmune diseases such as rheumatoid arthritis, lupus erythematosus and multiple sclerosis. Statins also have anti-oxidative and large-vessel endothelial supportive properties that occur independent of their lipid-lowering effects. Additionally, statins can suppress macrophage and microglial activation responsible for initiating inflammatory cytokine release. More than forty percent of adults aged 65 years or older use statins in the United States and Australia, a prevalence that increases with age. The effects of statin usage on ophthalmic practice are probably underrecognized. Cardiovascular disease and age-related macular degeneration (AMD) share common risk factors, consistent with the “vascular model” of AMD pathogenesis that implicates impaired choroidal circulation in Bruch’s membrane lipoprotein accumulation. AMD has a complex multifactorial pathogenesis involving oxidative stress, choroidal vascular dysfunction, dysregulated complement-cascade-mediated inflammation and pro-inflammatory and pro-angiogenic growth factors. Many of these components are hypothetically amenable to the primary (cholesterol lowering) and secondary (anti-inflammatory, anti-oxidative, anti-vasculopathy) effects of statin use. Experimental studies have been promising, epidemiological trails have produced conflicting results and three prospective clinical trials have been inconclusive at demonstrating the value of statin therapy for delaying or preventing AMD. Cumulative evidence to date has failed to prove conclusively that statins are beneficial for preventing or treating AMD.
Abstract: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease of childhood, and juvenile idiopathic associated uveitis (JIA-U) is the most frequently noted extra-articular manifestation. JIA-U can present asymptomatically and lead to ocular complications, so regular screening and monitoring are needed to prevent potentially sight-threatening sequelae. Topical glucocorticoids such as prednisolone acetate are usually the first line of treatment for anterior uveitis associated with JIA-U, but long-term use may be associated with cataract, ocular hypertension and glaucoma. Disease modifying anti-rheumatic drugs (DMARDs) such as methotrexate allow tapering of the corticosteroids to prevent long-term complications. Biologic therapies have been increasingly used as targeted therapies for JIA-U, particularly monoclonal antibodies targeting the proinflammatory cytokine TNF-α such as adalimumab and infliximab. One recent, multicenter, prospective, randomized clinical trial provided evidence of the efficacy of adalimumab with methotrexate for JIA-U compared to methotrexate alone. Another clinical trial studying the interleukin-6 inhibitor tocilizumab for JIA-U showed promise in tapering topical corticosteroids. Additionally, JAK inhibitors are emerging biologic therapies for JIA-U in patients refractory to TNF-α inhibitors, with a clinical trial assessing the efficacy of baricitinib for JIA-U underway. While clinical trials on these novel biologics are limited, further investigation of these agents may provide additional therapeutic options for JIA-U.
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: 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.
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.
