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1.
Adv Drug Deliv Rev ; 140: 33-50, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29777757

RESUMO

From the early days of cell biological research, the eye-especially the retina-has evoked broad interest among scientists. The retina has since been thoroughly investigated and numerous models have been exploited to shed light on its development, morphology, and function. Apart from various animal models and human clinical and anatomical research, stem cell-based models of animal and human cells of origin have entered the field, especially during the last decade. Despite the observation that the retina of different species comprises endogenous stem cells, most stem cell-related research in the human retina is now based on pluripotent stem cell models. Herein, systems of two-dimensional (2D) cultures and co-cultures of distinctly differentiated retinal subtypes revealed a variety of cellular aspects but have in many aspects been replaced by three-dimensional (3D) structures-the so-called retinal organoids. These organoids not only contain all major retinal cell subtypes compared to the physiological situation, but also show a distinct layering in close proximity to the in vivo morphology. Nevertheless, all these models have inherent advantages and disadvantages, which are expounded and summarized in this review. Finally, we discuss current application aspects of stem cell-based retina models and the specific promises they hold for the future.


Assuntos
Células-Tronco Pluripotentes Induzidas , Retina , Animais , Humanos , Modelos Biológicos
2.
Expert Opin Drug Discov ; 14(1): 47-57, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30526132

RESUMO

INTRODUCTION: Disorders of the eye that lead to visual impairment are affecting millions of people worldwide. Nevertheless, for many of these disorders, there are still no effective treatment options available due to the lack of in vitro model systems that emulate the physiological in vivo structure and function of human eyes. Microphysiological organ-on-a-chip (OoC) technology represents a novel and powerful approach to overcome the limitations of conventional model systems and lead to a paradigm shift in ophthalmic research. Areas covered: This review provides an overview of the various tissues of interest in ophthalmology and summarizes existing model systems, including their applications and limitations. Additionally, novel OoC systems with applications in ophthalmology are described and the advantages of these systems compared to conventional models are highlighted. Expert opinion: The physiological relevance of the first ophthalmic OoC systems that mimic human ocular compartments, such as the cornea and retina, has been successfully demonstrated in recent years. There is a great potential for the application of these platforms for future pharmacological target identification, safety, and efficacy testing, as well as personalized medicine. Further improvements and the development of new systems are of upmost importance, especially to model complex disorders affecting several tissues.


Assuntos
Descoberta de Drogas/métodos , Oftalmopatias/tratamento farmacológico , Dispositivos Lab-On-A-Chip , Administração Oftálmica , Animais , Humanos , Modelos Biológicos , Medicina de Precisão/métodos
3.
Front Mol Neurosci ; 10: 450, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29379414

RESUMO

A number of studies have reported changes in the hemispheric dominance in autism spectrum disorder (ASD) patients on functional, biochemical, and morphological level. Since asymmetry of the brain is also found in many vertebrates, we analyzed whether prenatal zinc deficient (PZD) mice, a mouse model with ASD like behavior, show alterations regarding brain lateralization on molecular and behavioral level. Our results show that hemisphere-specific expression of marker genes is abolished in PZD mice on mRNA and protein level. Using magnetic resonance imaging, we found an increased striatal volume in PZD mice with no change in total brain volume. Moreover, behavioral patterns associated with striatal lateralization are altered and the lateralized expression of dopamine receptor 1 (DR1) in the striatum of PZD mice was changed. We conclude that zinc signaling during brain development has a critical role in the establishment of brain lateralization in mice.

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