Photochemical Restoration of Light Sensitivity in the Degenerated Canine Retina
Abstract
:1. Introduction
2. Material and Methods
2.1. Animals
2.2. Intravitreal Injections with and without Prior Vitrectomy
2.3. MEA Recording
2.4. qRT-PCR
2.5. Histology and Immunohistochemistry
3. Results
3.1. MEA Analysis following Ex Vivo Application of DENAQ on Degenerated and WT Retinal Explants
3.2. Kinetics of DENAQ-Driven RGC Firing in Degenerated Retinas
3.3. MEA Analysis of Cone versus DENAQ-Driven RGC Firing
3.4. DENAQ Confers Light Sensitivity to Mutant Canine Retinas following Intravitreal Injection
3.5. P2X Receptors and HCN Channels Are Upregulated in Degenerated Canine Retinas
3.6. Dose-Dependent Focal Retinal Toxicity following Intravitreal Injection of DENAQ
3.7. Delivery of DENAQ in Vitrectomized Eyes Expands the Ocular Tolerance Range
4. Discussion
4.1. DENAQ Drives Light Responses in the Degenerated Canine Retinas
4.2. Repeated Light Stimuli Slow Activation and Accelerate Recovery of the DENAQ-Driven Responses
4.3. DENAQ can Override Responses of the Surviving Cones in the Degenerated Retinas
4.4. Switching off Retinal Synaptic Transmission Enhances DENAQ-Driven Response
4.5. Efficiency of DENAQ Treatment
4.6. DENAQ-Associated Ocular Toxicity
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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DENAQ Concentration | Visual Impairment | Ocular Discomfort | Anterior Uveitis | Glaucoma | Posterior Subcapsular Cataract | Posterior Uveitis | Retinal Detachment | Retinal Atrophy | Disrupted Retinal Lamination | Retinal Folds |
---|---|---|---|---|---|---|---|---|---|---|
10 mM | 2/4 | 2/4 | 4/4 | 1/4 | 4/4 | 2/4 | 1/4 | 2/4 | 2/4 | 0/4 |
5 mM | 6/6 * | 0/6 | 6/6 | 0/6 | 5/6 | 5/6 | 5/6 | 3/6 | 2/6 | 0/6 |
1 mM | 4/4 | 0/4 | 4/4 | 0/4 | 2/4 | 0/4 | 1/4 ** | 0/4 | 0/4 | 2/4 |
0.3 mM | 0/3 | 1/3 | 2/3 | 0/3 | 2/3 | 1/3 | 0/3 | 0/3 | 0/3 | 0/3 |
0.1 mM | 0/3 | 1/3 | 2/3 | 0/3 | 0/3 | 0/3 | 0/3 | 0/3 | 0/3 | 0/3 |
Vehicle *** | 0/2 | 0/2 | 2/2 | 0/2 | 0/2 | 0/2 | 0/2 | 0/2 | 0/2 | 0/2 |
DENAQ Concentration | Visual Impairment | Ocular Discomfort | Anterior Uveitis | Vitreal Hemorrhage | Retinal Detachment | Retinal Atrophy | Disrupted Retinal Lamination |
---|---|---|---|---|---|---|---|
10 mM | 1/3 | 3/3 | 3/3 | 0/3 | 3/3 | 1/2 | 1/2 |
3 mM | 2/3 * | 2/3 | 3/3 | 1/3 | 1/3 | 0/2 | 2/2 |
1 mM | 0/3 | 1/3 | 2/3 | 0/3 | 0/3 | 0/3 | 0/3 |
Vehicle ** | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 |
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Nikonov, S.; Dolgova, N.; Sudharsan, R.; Tochitsky, I.; Iwabe, S.; Guzman, J.-M.; Van Gelder, R.N.; Kramer, R.H.; Aguirre, G.D.; Beltran, W.A. Photochemical Restoration of Light Sensitivity in the Degenerated Canine Retina. Pharmaceutics 2022, 14, 2711. https://doi.org/10.3390/pharmaceutics14122711
Nikonov S, Dolgova N, Sudharsan R, Tochitsky I, Iwabe S, Guzman J-M, Van Gelder RN, Kramer RH, Aguirre GD, Beltran WA. Photochemical Restoration of Light Sensitivity in the Degenerated Canine Retina. Pharmaceutics. 2022; 14(12):2711. https://doi.org/10.3390/pharmaceutics14122711
Chicago/Turabian StyleNikonov, Sergei, Natalia Dolgova, Raghavi Sudharsan, Ivan Tochitsky, Simone Iwabe, Jose-Manuel Guzman, Russell N. Van Gelder, Richard H. Kramer, Gustavo D. Aguirre, and William A. Beltran. 2022. "Photochemical Restoration of Light Sensitivity in the Degenerated Canine Retina" Pharmaceutics 14, no. 12: 2711. https://doi.org/10.3390/pharmaceutics14122711