Neurodegeneration, Neuroprotection and Regeneration in the Zebrafish Retina

Abstract

Neurodegenerative retinal diseases, such as glaucoma and diabetic retinopathy, involve a gradual loss of neurons in the retina as the disease progresses. Central nervous system neurons are not able to regenerate in mammals, therefore, an often sought after course of treatment for neuronal loss follows a neuroprotective or regenerative strategy. Neuroprotection is the process of preserving the structure and function of the neurons that have survived a harmful insult; while regenerative approaches aim to replace or rewire the neurons and synaptic connections that were lost, or induce regrowth of damaged axons or dendrites. In order to test the neuroprotective effectiveness or the regenerative capacity of a particular agent, a robust experimental model of retinal neuronal damage is essential. Zebrafish are being used more often in this type of study because their eye structure and development is well-conserved between zebrafish and mammals. Zebrafish are robust genetic tools and are relatively inexpensive to maintain. The large array of functional and behavioral tests available in zebrafish makes them an attractive model for neuroprotection studies. Some common insults used to model retinal disease and study neuroprotection in zebrafish include intense light, chemical toxicity and mechanical damage. This review covers the existing retinal neuroprotection and regeneration literature in the zebrafish and highlights their potential for future studies.

Zebrafish Model in Ophthalmology to Study Disease Mechanism and Drug Discovery

“…The development of zebrafish eye is fairly rapid. Neurogenesis begins at 28 hpf, and zebrafish embryos possess visual function as early as 72 hpf [ 27 , 28 ]. The optic vesicle, which finally gives rise to the neural retina and the RPE, evaginates from the forebrain at around 12 hpf and remains attached to the forebrain through a transient structure called the optic stalk [ 3 ].…”

“…Neurodegeneration in the form of RGC death is well documented in glaucoma. The chemical or oxidative stress-induced retinal damage is related to RGC injury and used in zebrafish research [ 28 ]. For example, NMDA, an analog of L-glutamate and an excitatory neurotransmitter in the mammalian central nervous system, can induce cellular excitotoxicity and RGC loss, and then glaucoma and retinal neurodegeneration [ 78 ].…”

“…Interestingly, the zebrafish with the gnn mutant displays the AMD-related degeneration of red cones at around 5 dpf [ 106 ]. Additionally, the overexpression of HTRA1 , a protein involved in the pathophysiology of AMD, can induce an accumulation of lipofuscin and melanolipofuscin between the photoreceptor and RPE layers in zebrafish [ 28 ]. The transgenic overexpression of human HTRA1 in zebrafish displays certain morphologic changes of the RPE, photoreceptor cell death, and lipofuscin accumulation, which are the features of early AMD [ 107 ].…”

Zebrafish Models for the Safety and Therapeutic Testing of Nanoparticles with a Focus on Macrophages

“…Several zebrafish models have been established and optimized for the understanding of neuroinflammatory or neurodegenerative diseases [ 207 , 208 ]. In parallel, different types of NPs have been engineered for the treatment and/or diagnosis of neuro-related disorders [ 209 , 210 ].…”

“…In parallel, different types of NPs have been engineered for the treatment and/or diagnosis of neuro-related disorders [ 209 , 210 ]. Interestingly, zebrafish models have also been used to study the neurotoxic or neuroprotective effects of a wide variety of NPs and biomaterials [ 207 ]. Below, we provide some examples of investigations using zebrafish models and NPs to improve drug targeting and/or efficacy in the context of neuroinflammatory and neurodegenerative diseases ( Table 2 ).…”