Progressive Photoreceptor Dysfunction and Age-Related Macular Degeneration-Like Features in rp1l1 Mutant Zebrafish.

Area of Science:

• Ophthalmology
• Genetics
• Molecular Biology

Background:

• Photoreceptor diseases cause irreversible vision loss and blindness.
• Mutations in RP1L1 gene are linked to photoreceptor degenerations like occult macular dystrophy and retinitis pigmentosa.
• RP1L1 protein is crucial for photoreceptor axoneme structure.

Purpose of the Study:

• To develop and characterize a novel zebrafish model for RP1L1-associated photoreceptor disease.
• To investigate the functional and structural consequences of rp1l1 gene disruption in vivo.
• To explore the presence of age-related macular degeneration-like features in the developed model.

Main Methods:

• CRISPR/Cas9 genome editing was used to generate the rp1l1 zebrafish mutant.
• Electrophysiological assessments were performed to evaluate photoreceptor function.
• Optical coherence tomography and retinal histology were used to analyze retinal structure.

Main Results:

• The rp1l1 zebrafish mutant exhibited progressive photoreceptor functional deficits.
• Optical coherence tomography revealed gaps in the photoreceptor layer, disrupted mosaics, and retinal thinning.
• Mutant retinas showed disorganized outer segments and subretinal drusenoid deposits.

Conclusions:

• The generated rp1l1 zebrafish mutant serves as a valuable new model for studying RP1L1-associated photoreceptor diseases.
• This model recapitulates key features of human photoreceptor degeneration, including subretinal drusenoid deposits.
• The findings offer insights into the pathogenesis of RP1L1-linked vision loss and age-related macular degeneration.