Differences in Oxygen-Induced Retinopathy Susceptibility Between Two Sprague Dawley Rat Vendors: A Comparison of Retinal Transcriptomes

Abstract

Purpose

To determine the retinal transcriptomic differences underlying the oxygen-induced retinopathy phenotypes between Sprague Dawley rat pups from two commonly used commercial vendors. This will allow us to discover genes and pathways that may be related to differences in disease severity in similarly aged premature babies and suggest possible new treatment approaches.

Methods

We analyzed retinal vascular morphometry and transcriptomes from Sprague Dawley rat pups from Charles River Laboratories and Envigo (previously Harlan). Room air control and oxygen-induced retinopathy groups were compared. Oxygen-induced retinopathy was induced with the rat 50/10 model.

Results

Pups from Charles River Laboratories developed a more severe oxygen-induced retinopathy phenotype, with 3.6-fold larger percent avascular area at P15 and twofold larger % neovascular area at P20 than pups from Envigo. Changes in retinal transcriptomes of rat pups from both vendors were substantial at baseline and in response to oxygen-induced retinopathy. Baseline differences centered on activated pathways of neuronal development in Charles River Laboratories pups. In response to oxygen-induced retinopathy, during the neovascular phase, retinas from Charles River Laboratories pups exhibited activation of pathways regulating necrosis, neuroinflammation, and interferon signaling, supporting the observed increase of neovascularization. Conversely, retinas from Envigo pups showed decreased necrosis and increased focal adhesion kinase signaling, supporting more normal vascular development. Comparing oxygen-induced retinopathy transcriptomes at P15 to those at P20, canonical pathways such as phosphate and tensin homolog, interferon, and coordinated lysosomal expression and regulation element signaling were identified, highlighting potential novel mechanistic targets for future research.

Conclusion

Transcriptomic profiles differ substantially between rat pup retinas from Charles River Laboratories and Envigo at baseline and in response to oxygen-induced retinopathy, providing insight into vascular morphologic differences. Comparing transcriptomes identified new pathways for further research in oxygen-induced retinopathy pathogenesis and increased scientific rigor of this model.

Keywords:

• Oxygen induced retinopathy
• Sprague Dawley
• retinopathy of prematurity
• RNA sequencing
• animal vendor

Acknowledgements

The authors would like to acknowledge Juan E. Abrahante Lloréns, PhD of the University of Minnesota Informatics Institute who performed the pairwise comparisons generating the differentially expressed genes from the RNA sequencing data.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Raw data of all expressed genes from next generation RNA sequencing is available in Database: Mendeley Data: doi: 10.17632/xrjrnjmydt.

Additional information

Funding

This work was supported by the American Academy of Pediatrics under the Marshall Klaus Grant (no award number); and the Knights Templar Eye Foundation under the Career Starter Grant (no award number) to EI.