Long-Term Oral Treatment with Non-Hypoglycemic Dose of Glibenclamide Reduces Diabetic Retinopathy Damage in the Goto-KakizakiRat Model
Abstract
:1. Introduction
2. Material and Methods
2.1. Animals and Animal Model; Ethical Concerns
2.2. Long-Term Oral Glibenclamide Treatment
2.3. qPCR–ABCC8 Neuroretinal Expression
2.4. Electroretinography (ERG)—Visual Function Evaluation
2.5. Fundoscopy, Optical Coherence Tomography (OCT)—Neuroretinal Thickness Measurement
2.6. Fluorescein and Indocyanin Green Angiographies—Retinal and Choroidal Vascularization Imaging and Evaluation of Dye Vascular Infusion
2.7. Flatmounts, Immunohistochemistry and Home-Made Macro Analysis for Evaluation of Capillary Percentage among Retinal Vessels and RPE cell Areas Analysis
2.8. Statistics
3. Results
3.1. Long-Term Oral Glibenclamide at 200 µg/kg BID did Not Influence Body Weight and Glycemic Control in GK Rats–qPCR ABCC8 Expression
3.2. Long-Term Non-Hypoglycemic Oral Glibenclamide Treatment Improves Retinal Function in GK Rats
3.3. Long-Term Non-Hypoglycemic Oral Glibenclamide Treatment Reduces Retinal Edema in GK Rats
3.4. Long-Term Non-Hypoglycemic Oral Glibenclamide Improves Retinal Vascular Perfusion in Diabetic Goto-Kakizaki Rats
3.5. Long-Term Non-Hypoglycemic Oral Glibenclamide Prevented Outer Retinal Barrier Damages
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gene | Primer Reference | ||
---|---|---|---|
ABCC8 | TaqMan™Gene Expression Assay (FAM) Rn01476317_m1 | #4331182 | Life Technologie SAS |
GAPDH | TaqMan™Gene Expression Assay (FAM) Rn01775763_g1 | #4331182 | Life Technologie SAS |
Non-Diabetic Females | Diabetic | Diabetic + GLI | |||||||
---|---|---|---|---|---|---|---|---|---|
Age (Months) | Mean | SD | n | Mean | SD | n | Mean | SD | n |
2 | 4.94 | 0.3 | 5 | 6.28 | 0.64 | 8 | 5.96 | 1.33 | 5 |
6 | 4.6 | 0.27 | 3 | 9.15 | 0.65 | 8 | 7.74 | 2.05 | 5 |
12 | 5 | 0.27 | 3 | 10.62 | 1.63 | 8 | 9.125 | 1.6 | 4 |
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Berdugo, M.; Delaunay, K.; Lebon, C.; Naud, M.-C.; Radet, L.; Zennaro, L.; Picard, E.; Daruich, A.; Beltrand, J.; Kermorvant-Duchemin, E.; et al. Long-Term Oral Treatment with Non-Hypoglycemic Dose of Glibenclamide Reduces Diabetic Retinopathy Damage in the Goto-KakizakiRat Model. Pharmaceutics 2021, 13, 1095. https://doi.org/10.3390/pharmaceutics13071095
Berdugo M, Delaunay K, Lebon C, Naud M-C, Radet L, Zennaro L, Picard E, Daruich A, Beltrand J, Kermorvant-Duchemin E, et al. Long-Term Oral Treatment with Non-Hypoglycemic Dose of Glibenclamide Reduces Diabetic Retinopathy Damage in the Goto-KakizakiRat Model. Pharmaceutics. 2021; 13(7):1095. https://doi.org/10.3390/pharmaceutics13071095
Chicago/Turabian StyleBerdugo, Marianne, Kimberley Delaunay, Cécile Lebon, Marie-Christine Naud, Lolita Radet, Léa Zennaro, Emilie Picard, Alejandra Daruich, Jacques Beltrand, Elsa Kermorvant-Duchemin, and et al. 2021. "Long-Term Oral Treatment with Non-Hypoglycemic Dose of Glibenclamide Reduces Diabetic Retinopathy Damage in the Goto-KakizakiRat Model" Pharmaceutics 13, no. 7: 1095. https://doi.org/10.3390/pharmaceutics13071095