Loss of 15-Lipoxygenase in Retinodegenerative RCS Rats
Abstract
:1. Introduction
2. Results
2.1. Ocular PUFAs and Their Metabolites in Relation to Retinodegeneration
2.2. Correlations of Ocular PUFA Metabolites with Changes in Retinal Structure and Function
2.3. Ocular Metabolite Ratios and Retinal Lipoxygenase Gene Expression
2.4. RNA Sequencing and Ingenuity Pathway Analysis Predicts Declines of SPMs with Disease Progression in RCS Rats
2.5. NAP1051 IVT Administration Demonstrates Preservation of ONL Nuclei and Reductions in PAD4
2.6. Oral NAP1051 Administration Preserved Retinal Structure and Function
2.7. Effects of NAP1051 on Ocular Gene Expression
2.8. NAP1051 Impact on Lipidomics Analyses of RCS Rat Ocular Lipids
2.9. Oral NAP1051 Administration to rd10 Mice Preserved Retinal ONL PRs, Reduced FAF Appearance, and Reduced Markers of Inflammation and Oxidative Stress
3. Discussion
4. Materials and Methods
4.1. Animals
4.2. Natural Progression Study Design
4.3. Retinal RNA Sequencing and IPA Analyses
4.4. Intravitreal NAP1051 Study Design
4.5. Electroretinogram (ERG) Recordings
4.6. Tissue Isolation and Preparation of Histological Sections
4.7. ImageJ/FIJI Quantification of H&E ONL Nuclei, FAF Hyperpigmentation, and Retinal Layer Thickness
4.8. Immunofluorescent Staining
4.9. RNA Extraction from Ocular Tissue
4.10. cDNA Synthesis
4.11. Ocular qPCR
4.12. LC-MS/MS Lipidomics Assay
4.13. Statistical Analyses
4.14. Ethical Approval
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Mead, A.J.; Ahluwalia, K.; Ebright, B.; Zhang, Z.; Dave, P.; Li, Z.; Zhou, E.; Naik, A.A.; Ngu, R.; Chester, C.; et al. Loss of 15-Lipoxygenase in Retinodegenerative RCS Rats. Int. J. Mol. Sci. 2024, 25, 2309. https://doi.org/10.3390/ijms25042309
Mead AJ, Ahluwalia K, Ebright B, Zhang Z, Dave P, Li Z, Zhou E, Naik AA, Ngu R, Chester C, et al. Loss of 15-Lipoxygenase in Retinodegenerative RCS Rats. International Journal of Molecular Sciences. 2024; 25(4):2309. https://doi.org/10.3390/ijms25042309
Chicago/Turabian StyleMead, Andrew James, Kabir Ahluwalia, Brandon Ebright, Zeyu Zhang, Priyal Dave, Zeyang Li, Eugene Zhou, Aditya Anil Naik, Rachael Ngu, Catherine Chester, and et al. 2024. "Loss of 15-Lipoxygenase in Retinodegenerative RCS Rats" International Journal of Molecular Sciences 25, no. 4: 2309. https://doi.org/10.3390/ijms25042309