Zebrafish Models of Photoreceptor Ciliopathies
Pp. 16-38 (23)
Brian D. Perkins
Abstract
Ciliopathies refer to a genetically and clinically heterogeneous class of
disorders that result from defects in the formation or function of the primary cilium.
Cilia are the microtubule-based organelles that protrude from the surface of almost all
vertebrate cells, including the rod and cone photoreceptors. The photoreceptor sensory
cilium consists of the connecting cilium and outer segment with the outer segment
forming a unique structure containing thousands of tightly packed disc membranes.
Mutations in over 50 genes result in syndromic ciliopathies that can manifest with
retinal degeneration, including Bardet-Biedl syndrome (BBS), Joubert Syndrome,
Jeune Syndrome, and nephronophthisis (NPHP) or in non-syndromic retinal
dystrophies like Leber Congenital Amaurosis (LCA) and Retinitis Pigmentosa (RP).
Zebrafish have been widely used as a model system to study ciliopathies, particularly
BBS and Joubert Syndrome, and for studying the mechanisms leading to photoreceptor
degeneration associated with these disorders. Investigators were drawn to zebrafish due
to the rapid growth and transparency of the zebrafish embryo, the differentiation of
photoreceptors by 3 days post-fertilization, and the ability to suppress gene function
through morpholino knockdown. The genetic heterogeneity of ciliopathies and desire
for more accurate genotype-phenotype correlations make zebrafish an appealing model
for studying gene- and allele-specific differences in a rapid manner. This review will
discuss the current zebrafish models of retinal ciliopathies, evaluate the widespread use
of morpholinos as tools to knock down gene function in zebrafish, and make
predictions on how zebrafish will contribute in future studies of ciliopathies.
Keywords:
ahi1, arl13b, Bardet-Biedl Syndrome, BBS, cep290, Ciliopathies,
Cilium, Joubert Syndrome, Photoreceptor, Retina, Retinal Degeneration, Sensory
Cilium, Zebrafish.
Affiliation:
Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic, 9500 Euclid Ave. Cleveland, OH 44195, USA.