Zebrafish And Retinitis Pigmentosa

The zebrafish which are in good condition are selected and a chemical mutagen is used to induce random point mutation. It provide a powerful system to model RP, and they have been used to model a number of human retinal-degenerative diseases. 

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Zebrafish And Retinitis Pigmentosa

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How Retinitis pigmentosa is inherited?

  1. Autosomal recessive inheritance requires two copies of mutant gene to cause the disorder
  2. Autosomal dominant inheritance requires one copy of the gene because the disorder
  3. X-linked inheritance in this form of inheritance mutated X chromosome from mother gene is passed to their sons

How is it identified in zebrafish?

  1. Electroretinogram
  2. Visual field testing
  3. Genetic testing

Treatment

  1. Targeted gene therapy-Luxturna for the treatment of Lebar’s Congenital Amaurosis (LCA)
  2. There are no effective drug treatment 

Further we are going to see about carvedilol drug used for treating autosomal dominant disorder

Why do we use zebrafish?

  1. The zebrafish can provide a powerful system to model RP, and they have been used to model a number of human retinal-degenerative diseases. 
  2. These models include transgenic zebrafish expressing human rhodopsin (RHO) with autosomal dominant mutations found in RP patients
  3. Low cost of use, high fecundity, amenability to genetic manipulation
  4. The mutation used to induce RP in zebrafish is the Q344X gene.
  5. Here we utilized the Q344X zebrafish model to develop an in vivo drug-screening platform for identifying drugs that may treat adRP.

Mode of induction ?

Mode of induction ?

Identification of that mutation on larvae:

Q344X larvae were identified on 2 dpf through the expression of EGFP under the control of 1.1 kb promoter of olfactory marker protein (omp) .

Assay performed :

VMR assay:
VMR assay:

In a 96-well plate: Q344X transgenic larvae were identified and sorted at 2 dpf. These larvae were dark adapted overnight at 6 dpf and their VMR assessed at 7 dpf. These larvae were acclimated in darkness for 30 min exposed to the scotopic light of 0.01 lx for 60 min. Then exposed to darkness again .

Discussion :

The RP G-protein coupled receptor is over regulated leading to the change in CAMP and ADCH pathway that cause rod degeneration or disruption by apoptosis and also causes oxidative stress. Our main motto is to see whether oxidative stress produced during this pathway is reduced by this carvedilol drug we found carvedilol drug reduces this oxidative stress and has enhanced vision in Q334X larvae .So we suggest carvedilol drug is found to be effective in treating retinitis pigmentosa.

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