Copper induce zebrafish retinal developmental defects via triggering stresses and apoptosis

Area of Science:

• Developmental Biology
• Toxicology
• Ophthalmology

Background:

• Copper homeostasis is vital for development; disruptions cause disease.
• Excess copper nanoparticles (CuNPs) and ions (Cu2+) can lead to developmental malformations.
• Mechanisms linking excess copper to retinal developmental defects remain largely unknown.

Purpose of the Study:

• To investigate the mechanisms by which excess copper induces retinal developmental malformation.
• To identify the role of oxidative stress, endoplasmic reticulum stress, and apoptosis in copper-induced retinal defects.
• To determine the necessity of copper transporters Cox17 and Atp7a in these processes.

Main Methods:

• Zebrafish embryos were exposed to copper (CuNPs and Cu2+).
• Cell proliferation, apoptosis, reactive oxygen species (ROS), and endoplasmic reticulum (ER) stress were assessed.
• Genetic mutants (cox17-/- and atp7a-/-) were utilized to study copper transport.

Main Results:

• Copper exposure reduced retinal cell numbers and downregulated retinal gene expression.
• ER and mitochondrial structures were damaged, with increased ROS, unfolded protein responses (UPR), and apoptosis.
• ROS scavengers (GSH, NAC) and an ER stress inhibitor (PBA) mitigated copper-induced defects.
• Deletion of cox17 or atp7a genes alleviated retinal defects under copper stress.

Conclusions:

• Copper nanoparticles and ions induce zebrafish embryonic retinal defects by upregulating UPR and ROS, leading to apoptosis.
• The integrated function of copper transporters Cox17 and Atp7a is essential for copper-induced retinal defects.