Zebrafish Models of Photoreceptor Dysfunction and Degeneration

Abstract

Zebrafish are an instrumental system for the generation of photoreceptor degeneration models, which can be utilized to determine underlying causes of photoreceptor dysfunction and death, and for the analysis of potential therapeutic compounds, as well as the characterization of regenerative responses. We review the wealth of information from existing zebrafish models of photoreceptor disease, specifically as they relate to currently accepted taxonomic classes of human rod and cone disease. We also highlight that rich, detailed information can be derived from studying photoreceptor development, structure, and function, including behavioural assessments and in vivo imaging of zebrafish. Zebrafish models are available for a diversity of photoreceptor diseases, including cone dystrophies, which are challenging to recapitulate in nocturnal mammalian systems. Newly discovered models of photoreceptor disease and drusenoid deposit formation may not only provide important insights into pathogenesis of disease, but also potential therapeutic approaches. Zebrafish have already shown their use in providing pre-clinical data prior to testing genetic therapies in clinical trials, such as antisense oligonucleotide therapy for Usher syndrome.

Zebrafish Model in Ophthalmology to Study Disease Mechanism and Drug Discovery

“…Zebrafish retina is made up of an outer nuclear layer (ONL), outer plexiform layer (OPL), inner nuclear layer (INL), inner plexiform layer (IPL), and ganglion cell layer (GCL). It also possesses the same broad classes of retinal neurons in humans, such as retinal ganglion cells (RGC), bipolar cells, horizontal cells, and amacrine cells, and the same glial elements including Müller cells, astrocytes, and microglia ( Figure 1 ) [ 6 , 13 ]. Furthermore, the zebrafish retina is cone-rich and analogous to the human macula, which results in good color vision and high-acuity vision [ 13 ].…”

“…It also possesses the same broad classes of retinal neurons in humans, such as retinal ganglion cells (RGC), bipolar cells, horizontal cells, and amacrine cells, and the same glial elements including Müller cells, astrocytes, and microglia ( Figure 1 ) [ 6 , 13 ]. Furthermore, the zebrafish retina is cone-rich and analogous to the human macula, which results in good color vision and high-acuity vision [ 13 ]. In addition, zebrafish has four types of cones: blue ( sws2 ), ultraviolet ( sws1 ), green ( rh2 ), and red ( lws ), among which the green and red cones exist as a physically fused double cones [ 13 , 14 ].…”

“…In this review, we highlighted the use of zebrafish in modeling eye diseases by (i) introducing the characteristic anatomy and development of zebrafish eye, (ii) summarizing zebrafish models of eye diseases, such as cornea dystrophy, cataract, glaucoma, ocular green (rh2), and red (lws), among which the green and red cones exist as a physically fused double cones [13,14]. Visual signals arising from the photoreceptors are transmitted through the whole retina to the ganglion cells and subsequently transferred to the brain [3].…”

“…horizontal cells, and amacrine cells, and the same glial elements including Müller cells, astrocytes, and microglia (Figure 1) [6,13]. Furthermore, the zebrafish retina is cone-rich and analogous to the human macula, which results in good color vision and high-acuity vision [13].…”

Retinal Stem Cell ‘Retirement Plans’: Growth, Regulation and Species Adaptations in the Retinal Ciliary Marginal Zone

“…This is because, despite the ability of zebrafish to continually produce new retinal neurons at the margin and even regenerate central neurons through Müller glia activation [ 10 , 133 ], the zebrafish retina is still vulnerable to retinal pathologies. In fact, many retinal degenerative conditions have been faithfully modelled using zebrafish [ 134 , 135 ], and retinal injury does not affect the proliferation rate or mode of division (i.e., asymmetric division) of RSCs in the CMZ [ 41 ], suggesting that the CMZ is mostly unresponsive to these types of injury cues. In regeneration-capable species, including teleost fish and amphibians, the CMZ does not appear to be the primary source of RSCs that are induced to respond to retinal injury.…”