Zebrafish—on the move towards ophthalmological research

Abstract

Millions of people are affected by visual impairment and blindness globally, and the prevalence of vision loss is likely to increase as we are living longer. However, many ocular diseases remain poorly controlled due to lack of proper understanding of the pathogenesis and the corresponding lack of effective therapies. Consequently, there is a major need for animal models that closely mirror the human eye pathology and at the same time allow higher-throughput drug screening approaches. In this context, zebrafish as an animal model organism not only address these needs but can in many respects reflect the human situation better than the current rodent models. Over the past decade, zebrafish have become an established model to study a variety of human diseases and are more recently becoming a valuable tool for the study of human ophthalmological disorders. Many human ocular diseases such as cataract, glaucoma, diabetic retinopathy, and age-related macular degeneration have already been modelled in zebrafish. In addition, zebrafish have become an attractive model for pre-clinical drug toxicity testing and are now increasingly used by scientists worldwide for the discovery of novel treatment approaches. This review presents the advantages and uses of zebrafish for ophthalmological research.

Quantitative biometry of zebrafish retinal vasculature using optical coherence tomographic angiography

“…Similar to humans, the zebrafish retina is composed of seven major cell types (Müller glia and six neural cell types), three nuclear layers separated by two plexiform layers, and a highly ordered mosaic of neurons in each layer [19,20]. As diurnal species, humans and zebrafish both have cone-dominant vision, in contrast to rod-dominant vision found in mice, which has advantages for studying cone degeneration diseases such as AMD [20,21].…”

“…Retinal vasculopathies can be modeled by exposing animals to hypoxic water for 3-10 days to induce neovascularization and vascular leakage [21]. Similarly, exposure to glucose induces hyperglycemia, which has been shown to result in retinal structure abnormalities similar to those in DR [21].…”

“…Retinal vasculopathies can be modeled by exposing animals to hypoxic water for 3-10 days to induce neovascularization and vascular leakage [21]. Similarly, exposure to glucose induces hyperglycemia, which has been shown to result in retinal structure abnormalities similar to those in DR [21]. As a pharmacological model, 82% of disease-causing human proteins have orthologues in zebrafish, and pharmacological effects are highly conserved between humans and zebrafish [23][24][25].…”

Autonomous system for cross-organ investigation of ethanol-induced acute response in behaving larval zebrafish

“…These changes in the eye movements indicated that acute ethanol treatment may impair the vision function in zebrafish larvae. 13,32 D. Analysis of cardiac function in response to ethanol treatment…”

Imaging, manipulation and optogenetics in zebrafish

“…They also have small brains that are well suited to studies FIGURE 1.1: Top and side view of a 6 days post-fertilization (dpf) larvae zebrafish using light-based techniques. Despite the brain's size, larvae at 5 days postfertilisation (dpf) have functioning sensory systems for visual [11][12][13], auditory [14][15][16], somatory [17,18], water flow [19][20][21], and vestibular stimuli [22,23]. This makes them an ideal system in which to use light based tools to study the details of sensory neural circuits.…”