Customized In Vivo Ocular Models ace

Customized Zebrafish Models of Cone-Rod Dystrophy

The zebrafish is a tool system for generating models of photoreceptor degeneration that can be used to determine the underlying causes of photoreceptor dysfunction and death and for the analysis of potential therapeutic compounds and the characterization of regenerative responses. Ace Therapeutics is providing our customers with a high-quality zebrafish cone-rod dystrophy model by exploring the mutated genes associated with cone-rod dystrophy in humans and zebrafish. These models help gain insight into blindness conditions associated with cone-rod dystrophy and uncover possible treatments.

Zebrafish Models of Cone Rod Dystrophy

What Is Cone-Rod Dystrophy?

Visual defects will have a significant negative impact on human life quality and cause a significant economic burden. Cone-rod dystrophy is a group of inherited vision-deficient ocular diseases that affect the photoreceptor cells of the retina called cones and rods, the layer of light-sensitive tissue at the back of the eye. Degeneration of the cones and rods will result in weakened vision, eventually leading to vision loss. Studies have shown that cone-rod dystrophy causes large genetic mutations, at least 30. Therefore, flexible animal model systems are needed to study possible blinding conditions and treatments associated with this group of diseases. Zebrafish eyes are structurally and functionally similar to humans. They are valuable vertebrate model organisms, which have been widely used in the study of genetic and environmental eye diseases.

Fig. 1. Anatomy of rod and cone photoreceptors and their organization in the human retina. (Noel NCL, et al., 2021)

Service Overview

Cone-rod dystrophy is an ocular disorder that affects photoreceptors and clinically manifests by damage to the retinal pigment epithelium. In recent years, Ace Therapeutics aims to develop a full range of eye disease models to meet global researchers' needs. Thanks to extensive experience in the field of ocular diseases, as well as in human zebrafish genomics, our scientists have made considerable progress in elucidating the molecular genetics and genotype-phenotype correlations associated with these dystrophies, and have explored various zebrafish cone-rod dystrophy models.

Explore Ace Therapeutics' Zebrafish Models of Cone-Rod Dystrophy

Ace Therapeutics provides global customers with a transgenic zebrafish cone-rod dystrophy model. The phenomenon of cone survival in this zebrafish model offers an opportunity to study how cones respond to rod loss. It may provide insight into human factors in RP cone cell death.

In addition, Ace Therapeutics has also developed a series of zebrafish gene mutant cone-rod dystrophy models. Our scientists induce zebrafish to produce similar to human cone-rod dystrophy-associated phenotypes through genetic screening and genome editing strategies (knockout or knock-in of a specific gene).

It is worth mentioning that, in some cases, the disease phenotypes of these zebrafish mutant models may differ from those observed in human patients with mutations in the same gene. This may be due to differences in genetic lesion types. Loss-of-function mutations are most commonly engineered in animal models, but pathogenic mutations observed in humans may be missense, splice-site, or compound mutations.

Ace Therapeutics provides the following zebrafish cone-rod dystrophy models to customers around the world, including but not limited to:

Tab.1. Ace Therapeutics' zebrafish models (transgenic and mutant) of cone-rod dystrophy.

Gene	Photoreceptor + RPE Features
Tg(3.2gnat2:hsa.GUCY2D-E837D R838S)	Dysmorphic cones at 5 dpf. 3-month-old animals have a thin photoreceptor layer in the central retina, dysmorphic cones, and less cone and rod staining.
ahi1	Disorganized, short outer segments, but normal visual function at 5 dpf. Thin photoreceptor nuclear layer, cone degeneration.
arl13b	Short outer segments at 4dpf. Cone degeneration observed at 30 dpf in mosaic animals.
bbs2	Short, disorganized photoreceptor outer segments and visual deficits at 5 dpf. Photoreceptor degeneration observed in adulthood.
cc2d2a	Dysmorphic photoreceptor outer segments and functional defects at 5 dpf.
eys	Progressive photoreceptor loss; cone degeneration observed at 6 months, rod degeneration observed at 14 months.
kcnj13	Increased phagosomes in the RPE at 3 months, enlarged RPE mitochondria at 6 months, and abnormal melanosome localization under dark adaptation at 12 months. Cone mitochondria abnormalities at 6 months and photoreceptor loss at 12 months.
lca5	Photoreceptor functional defects at 7 dpf. Cone outer segment defects at 1 month, rod outer segment defects at 7 months, and progressive photoreceptor loss.
pcare1	Dysmorphic outer segments and dysfunctional photoreceptors at 5 dpf. Abnormal outer segments morphology and thinner photoreceptor layer at 6 months.
pomgnt1	Reduction in cones and rods at 6 months.

Ace Therapeutics aims to provide a powerful analytical tool to help our global customers study blinding mechanisms and potential therapeutic strategies associated with cone-rod dystrophy. If you are interested in our services or need more detailed information, please feel free to contact us. Our experienced scientists are ready to help you!

References

Hamel CP. Cone rod dystrophies. Orphanet J Rare Dis. 2007, 2:7.
Noel NCL, MacDonald IM, Allison WT. Zebrafish Models of Photoreceptor Dysfunction and Degeneration. Biomolecules. 2021, 11(1):78.

For Research Use Only.

Get in Touch