Neuroprotective effect of the calcium channel blocker nilvadipine on retinal ganglion cell death in a mouse ocular hypertension model
We investigated whether nilvadipine has a neuroprotective effect on retinal ganglion cells (RGCs) in a mouse model of ocular hypertension (OH) that expresses cyan fluorescein protein (CFP) in RGCs. OH was induced in the right eyes of Thy1-CFP transgenic mice using a laser. Nilvadipine or vehicle tre...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023010198 |
| _version_ | 1797851949127696384 |
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| author | Hidekazu Tsuruga Hiroshi Murata Makoto Araie Makoto Aihara |
| author_facet | Hidekazu Tsuruga Hiroshi Murata Makoto Araie Makoto Aihara |
| author_sort | Hidekazu Tsuruga |
| collection | DOAJ |
| description | We investigated whether nilvadipine has a neuroprotective effect on retinal ganglion cells (RGCs) in a mouse model of ocular hypertension (OH) that expresses cyan fluorescein protein (CFP) in RGCs. OH was induced in the right eyes of Thy1-CFP transgenic mice using a laser. Nilvadipine or vehicle treatment began simultaneously with OH modeling and was administered intraperitoneally once daily for 8 weeks. Intraocular pressure (IOP) in both the laser- and non-treated eyes was measured weekly with the microneedle method, and calculations were performed to estimate the pressure insult in each eye. Using a retinal whole mount, the number of RGCs was counted at week 9. Laser-treated eyes showed a significant increase in IOP (p < 0.01), and the pressure insult did not differ between the drug-treated groups. Over time, laser treatment produced a significant decrease in the number of RGCs in the vehicle-treated groups, but this effect was attenuated by nilvadipine treatment. The pressure insult and RGC survival rate were significantly negatively correlated in the vehicle-treated group (y = -0.078 x + 107.8, r = 0.76, p < 0.001), but not in the nilvadipine-treated group (y = -0.015 x + 99.9, r = 0.43, p = 0.128). Nilvadipine was a potent neuroprotective agent for RGCs in our mouse model of OH and may have potential for protection against glaucoma. This model is useful as a screening tool for drugs with retinal protective effects. |
| first_indexed | 2024-04-09T19:26:07Z |
| format | Article |
| id | doaj.art-e851c0bb713b4ae6beda8e383be18f56 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-09T19:26:07Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-e851c0bb713b4ae6beda8e383be18f562023-04-05T08:16:57ZengElsevierHeliyon2405-84402023-03-0193e13812Neuroprotective effect of the calcium channel blocker nilvadipine on retinal ganglion cell death in a mouse ocular hypertension modelHidekazu Tsuruga0Hiroshi Murata1Makoto Araie2Makoto Aihara3Department of Ophthalmology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, JapanDepartment of Ophthalmology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, JapanDepartment of Ophthalmology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, JapanCorresponding author. Department of Ophthalmology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.; Department of Ophthalmology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, JapanWe investigated whether nilvadipine has a neuroprotective effect on retinal ganglion cells (RGCs) in a mouse model of ocular hypertension (OH) that expresses cyan fluorescein protein (CFP) in RGCs. OH was induced in the right eyes of Thy1-CFP transgenic mice using a laser. Nilvadipine or vehicle treatment began simultaneously with OH modeling and was administered intraperitoneally once daily for 8 weeks. Intraocular pressure (IOP) in both the laser- and non-treated eyes was measured weekly with the microneedle method, and calculations were performed to estimate the pressure insult in each eye. Using a retinal whole mount, the number of RGCs was counted at week 9. Laser-treated eyes showed a significant increase in IOP (p < 0.01), and the pressure insult did not differ between the drug-treated groups. Over time, laser treatment produced a significant decrease in the number of RGCs in the vehicle-treated groups, but this effect was attenuated by nilvadipine treatment. The pressure insult and RGC survival rate were significantly negatively correlated in the vehicle-treated group (y = -0.078 x + 107.8, r = 0.76, p < 0.001), but not in the nilvadipine-treated group (y = -0.015 x + 99.9, r = 0.43, p = 0.128). Nilvadipine was a potent neuroprotective agent for RGCs in our mouse model of OH and may have potential for protection against glaucoma. This model is useful as a screening tool for drugs with retinal protective effects.http://www.sciencedirect.com/science/article/pii/S2405844023010198GlaucomaNeuroprotectionNilvadipineCalcium channel blockerMouse |
| spellingShingle | Hidekazu Tsuruga Hiroshi Murata Makoto Araie Makoto Aihara Neuroprotective effect of the calcium channel blocker nilvadipine on retinal ganglion cell death in a mouse ocular hypertension model Heliyon Glaucoma Neuroprotection Nilvadipine Calcium channel blocker Mouse |
| title | Neuroprotective effect of the calcium channel blocker nilvadipine on retinal ganglion cell death in a mouse ocular hypertension model |
| title_full | Neuroprotective effect of the calcium channel blocker nilvadipine on retinal ganglion cell death in a mouse ocular hypertension model |
| title_fullStr | Neuroprotective effect of the calcium channel blocker nilvadipine on retinal ganglion cell death in a mouse ocular hypertension model |
| title_full_unstemmed | Neuroprotective effect of the calcium channel blocker nilvadipine on retinal ganglion cell death in a mouse ocular hypertension model |
| title_short | Neuroprotective effect of the calcium channel blocker nilvadipine on retinal ganglion cell death in a mouse ocular hypertension model |
| title_sort | neuroprotective effect of the calcium channel blocker nilvadipine on retinal ganglion cell death in a mouse ocular hypertension model |
| topic | Glaucoma Neuroprotection Nilvadipine Calcium channel blocker Mouse |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023010198 |
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