| First Author | Lankford L | Year | 2024 |
| Journal | Exp Eye Res | Volume | 241 |
| Pages | 109835 | PubMed ID | 38373629 |
| Mgi Jnum | J:345801 | Mgi Id | MGI:7611528 |
| Doi | 10.1016/j.exer.2024.109835 | Citation | Lankford L, et al. (2024) Influence of the calcium voltage-gated channel auxiliary subunit (CACNA2D1) absence on intraocular pressure in mice. Exp Eye Res 241:109835 |
| abstractText | The etiology of elevated intraocular pressure (IOP), a major risk factor for glaucoma (optic nerve atrophy), is poorly understood despite continued efforts. Although the gene variant of CACNA2D1 (encoding alpha2delta1), a calcium voltage-gated channel auxiliary subunit, has been reported to be associated with primary open-angle glaucoma, and the pharmacological mitigation of alpha2delta1 activity by pregabalin lowers IOP, the cellular basis for alpha2delta1 role in the modulation of IOP remains unclear. Our recent findings reveled readily detectable levels of alpha2delta1 and its ligand thrombospondin in the cytoskeletome fraction of human trabecular meshwork (TM) cells. To understand the direct role of alpha2delta1 in the modulation of IOP, we evaluated alpha2delta1 null mice for changes in IOP and found a moderate ( approximately 10%) but significant decrease in IOP compared to littermate wild type control mice. Additionally, to gain cellular insights into alpha2delta1 antagonist (pregabalin) induced IOP changes, we assessed pregabalin's effects on human TM cell actin cytoskeletal organization and cell adhesive interactions in comparison with a Rho kinase inhibitor (Y27632), a known ocular hypotensive agent. Unlike Y27632, pregabalin did not have overt effects on cell morphology, actin cytoskeletal organization, or cell adhesion in human TM cells. These results reveal a modest but significant decrease in IOP in alpha2delta1 deficient mice, and this response appears to be not associated with the contractile and cell adhesive characteristics of TM cells based on the findings of pregabalin effects on isolated TM cells. Therefore, the mechanism by which pregabalin lowers IOP remains elusive. |
