Dose and time response study to develop retinal degenerative model of zebrafish with lead acetate

Abstract

Objective: Animal models are the silent scouts that help to understand the complex biological processes and gather data that aid our understanding of how organisms function. Various animal models are being sacrificed to assess the impact of toxic chemicals. Mortality calculations should be minimised and much data should be collected on the basis of clinical signs that can contribute to identifying robust humane endpoints linked to mortality. This study was designed to calculate the lowest possible dose of PbAc (lead acetate), a neurotoxicant, that can have a toxicological impact on the zebrafish retina and to minimise animal usage. Dose and time-dependent changes were observed in the zebrafish retina following PbAc exposure with zero mortality. Vision and visual behaviour response are the foremost indicators that can be recorded to mark the risk assessment of any chemical. Therefore, the present study aims at dose and time response to find the lowest dose of PbAc affecting the zebrafish retina and its visual behaviour.

Materials and methods: Zebrafish were treated for 3 weeks with four concentrations of 0.04, 0.06, 0.08, and 0.1 mg/L of PbAc for a dose-response study. Then for the time response study, two doses 0.08 and 0.1 mg/L were selected and zebrafish were exposed to those concentrations for 2 and 4 weeks.

Results: The results of qualitative and quantitative analyses of retinal histology showed that 15 days of treatment with 0.08 mg/L concentration can cause appropriate damage to the photoreceptor layer. At the ultrastructural level, it was further observed that PbAc induces damage to the photoreceptors, especially the rod cells. Escape response sbehaviour showed a significant decrease in visual response to changing contrasts in an increasing dose-dependent manner.

Conclusion: In conclusion, it has been shown that 15 days treatment with 0.08 mg/L lead acetate induce retinal degeneration in zebrafish without causing any mortality.

Keywords:

• Retinal degeneration
• photoreceptor
• zebrafish
• lead acetate
• dose-time response

Author contributions

R.K. and V.G. equally contributed in research design, experimental work, drafting of manuscript and final analysis of manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

We are grateful to University Grants Commission (UGC) New Delhi for the award of Junior Research Fellowship [Sr. No. 2061630530]. This work was funded in part by Centre for Advanced Studies (CAS-UGC-New Delhi), Promotion of University Research and Scientific Excellence (PURSE-DST-New Delhi), University Grants Commission Basic Scientific Research UGC BSR (UGC-New Delhi), Fund for Improvement of S&T Infrastructure FIST (DST-New Delhi) and Sophisticated Analysis Instrumentation Facility (SAIF), Panjab University, Chandigarh).