Zebrafish Model in Ophthalmology to Study Disease Mechanism and Drug Discovery

Abstract

Visual impairment and blindness are common and seriously affect people’s work and quality of life in the world. Therefore, the effective therapies for eye diseases are of high priority. Zebrafish (Danio rerio) is an alternative vertebrate model as a useful tool for the mechanism elucidation and drug discovery of various eye disorders, such as cataracts, glaucoma, diabetic retinopathy, age-related macular degeneration, photoreceptor degeneration, etc. The genetic and embryonic accessibility of zebrafish in combination with a behavioral assessment of visual function has made it a very popular model in ophthalmology. Zebrafish has also been widely used in ocular drug discovery, such as the screening of new anti-angiogenic compounds or neuroprotective drugs, and the oculotoxicity test. In this review, we summarized the applications of zebrafish as the models of eye disorders to study disease mechanism and investigate novel drug treatments.

The BDNF/TrkB Neurotrophin System in the Sensory Organs of Zebrafish

“…For all these reasons, zebrafish are employed as a model to study different human sensory disorders. Zebrafish have been established as a valuable model for the study of the development and regeneration of retinal cells, [ 42 ] and have been largely used as a model in ophthalmology [ 43 ]. Genetic screens in zebrafish helped, not only to establish additional genetic models for photoreceptor degenerations but also to identify additional genes involved in retinal degeneration.…”

The Function and the Affecting Factors of the Zebrafish Gut Microbiota

“…First, it is believed that the composition of gut microbiota and its metabolites and derivatives all play a role in the metabolic homeostasis of the host ( Falcinelli et al, 2015 ), but various endogenous and exogenous factors affect the composition and abundance of the microbiota and it is quite difficult to dissect well the gut microbial-host interactions ( Brugman et al, 2009 ; Roeselers et al, 2011 ; Mottaz et al, 2017 ; Yang et al, 2017 ). Second, although zebrafish are an excellent model organism that has been used to study blood diseases ( Haffter et al, 1996 ; Langenau et al, 2003 ; Dooley et al, 2008 ; van Rooijen et al, 2009 ; Taylor and Zon, 2011 ; Santoriello and Zon, 2012 ), cancer ( Amatruda et al, 2002 ; Ignatius and Langenau, 2009 ; Mione and Trede, 2010 ; Ceol et al, 2011 ; Liu and Leach, 2011 ), heart diseases ( Chen et al, 1996 ; Stainier et al, 1996 ; Poss et al, 2002 ; Poss, 2007 ; Tang et al, 2019 ; Mukherjee et al, 2021 ), muscle disorders ( Bassett and Currie, 2003 ; Follo et al, 2013 ), kidney diseases ( Tobin and Beales, 2008 ; Diep et al, 2011 ; Sander and Davidson, 2014 ; Gehrig et al, 2018 ; Brilli et al, 2019 ), central nervous system diseases ( Stewart et al, 2015 ; Heylen et al, 2021 ), and eye diseases ( Ohnesorge et al, 2019 ; Hong and Luo, 2021 ), zebrafish does have certain disadvantages in mimicking human diseases. These disadvantages include the inclusion of many gene duplications in the zebrafish genome; the phenotypic characteristics of diseases caused by direct homologous genes may differ in zebrafish and humans ( Santoriello and Zon, 2012 ).…”

Zebrafish models of inherited retinal dystrophies

“…Since being established as an animal model for developmental genetics in the 1970s [19,20] , zebrafish have become increasingly popular as a disease model, including as a model for IRDs [21][22][23][24][25][26][27][28] . Investigators initially used genetic screens of fish mutagenized by ethylnitrosourea (ENU) to identify dozens of mutants with defects in retinal structure and function [29][30][31][32][33] .…”

“…Studies of zebrafish mutants with photoreceptor dysfunction during larval stages have provided valuable information regarding photoreceptor biology; however, in order to harness the capacity for regeneration in a diseased retina, it will be critical to investigate zebrafish models that mimic the pathology and progressive degeneration observed in human IRDs. Several recent reviews provide excellent discussions of regeneration [ 43 – 46 ] and of zebrafish mutants with retinal degeneration [ 22 , 27 , 47 – 49 ] .…”