Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2026
Vatinoxan Prevents Medetomidine-Associated Exophthalmos and Increased Glucose Concentrations in Blood and Aqueous Humor in Rats.
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Mustikka Minna P, Lindh Emily K-M, Alm Karoliina, Meller Anna S, Syrjä Pernilla E S, Pot Simon A, Raekallio Marja R, Honkavaara Juhana
Аннотация
PURPOSE: To evaluate whether vatinoxan, a peripherally selective alpha2-adrenoceptor antagonist, prevents the acute, medetomidine-associated ophthalmic changes in rats.
METHODS: Adult male Wistar rats (n = 9 in each group) were randomly allocated to receive subcutaneous medetomidine 0.4 mg/kg and midazolam 2 mg/kg (MM), MM with vatinoxan 8 mg/kg (MM-V), or MM with regular insulin 1 IU/kg (MM-I). Macroscopic photography (to assess globe position) and slit-lamp biomicroscopy were performed, and blood glucose (BG) concentration, intraocular pressure (IOP), and central corneal thickness (CCT) were measured at intervals until 50 min post-treatment. Surgical anesthesia was then induced, and aqueous humor glucose (AHG) concentration was measured prior to euthanasia.
RESULTS: In MM and MM-I, exophthalmos worsened over time (P < 0.05) and compared to MM-V (P ≤ 0.04 for both). BG increased significantly over time (P < 0.001) only in MM, and AHG was significantly higher in MM than in MM-V and MM-I (P < 0.001). Lens clarity was decreased at 50 min in both MM (P = 0.002) and MM-I (P = 0.048), compared to MM-V. CCT was greater in MM-V than in MM at 50 min (P = 0.02). Corneal clarity remained unchanged. IOP declined in all groups but remained significantly higher in MM-V 10 min versus 50 min post-treatment (P = 0.02).
CONCLUSIONS: Vatinoxan prevented pathological exophthalmos, lens opacification, the acute decline in IOP, hyperglycemia, and increased AHG in rats sedated with medetomidine-midazolam. Insulin similarly prevented hyperglycemia, but none of the ophthalmic changes. Acute alpha2-adrenoceptor agonist-mediated ophthalmic pathologies are independent from glycemic control.
METHODS: Adult male Wistar rats (n = 9 in each group) were randomly allocated to receive subcutaneous medetomidine 0.4 mg/kg and midazolam 2 mg/kg (MM), MM with vatinoxan 8 mg/kg (MM-V), or MM with regular insulin 1 IU/kg (MM-I). Macroscopic photography (to assess globe position) and slit-lamp biomicroscopy were performed, and blood glucose (BG) concentration, intraocular pressure (IOP), and central corneal thickness (CCT) were measured at intervals until 50 min post-treatment. Surgical anesthesia was then induced, and aqueous humor glucose (AHG) concentration was measured prior to euthanasia.
RESULTS: In MM and MM-I, exophthalmos worsened over time (P < 0.05) and compared to MM-V (P ≤ 0.04 for both). BG increased significantly over time (P < 0.001) only in MM, and AHG was significantly higher in MM than in MM-V and MM-I (P < 0.001). Lens clarity was decreased at 50 min in both MM (P = 0.002) and MM-I (P = 0.048), compared to MM-V. CCT was greater in MM-V than in MM at 50 min (P = 0.02). Corneal clarity remained unchanged. IOP declined in all groups but remained significantly higher in MM-V 10 min versus 50 min post-treatment (P = 0.02).
CONCLUSIONS: Vatinoxan prevented pathological exophthalmos, lens opacification, the acute decline in IOP, hyperglycemia, and increased AHG in rats sedated with medetomidine-midazolam. Insulin similarly prevented hyperglycemia, but none of the ophthalmic changes. Acute alpha2-adrenoceptor agonist-mediated ophthalmic pathologies are independent from glycemic control.