Dataset Information

Topical Application of Bunazosin Hydrochloride Suppresses Myopia Progression With an Increase in Choroidal Blood Perfusion.

ABSTRACT:

Purpose

The incidence of myopia has rapidly increased in recent decades, making it a growing public health concern worldwide. Interventions to suppress the progression of myopia are needed; one suggested strategy is the prevention of choroidal thinning, which can improve choroidal blood perfusion (ChBP). Bunazosin hydrochloride (BH) is an alpha1-adrenergic blocker and commercialized glaucoma eye drop that increases in blood circulation in the eye. In this study, we evaluated the efficacy of BH in suppressing the progression of myopia in a lens-induced murine model.

Methods

Lens-induced myopia was induced in 3-week-old C57BL/6 J mice with -30 diopter (D) lenses for three weeks. Refractive error, axial length, and choroidal thickness were evaluated at three and six weeks of age using an infrared photorefractor and a spectral domain optical coherence tomography (OCT) system. Moreover, ChBP and scleral thickness were evaluated using swept-source OCT and histological analysis.

Results

Compared with the controls, the administration of BH eye drops suppressed the myopic shift of refractive error (mean difference ± standard error in the eye with -30 D lens, -13.65 ± 5.69 D vs. 2.55 ± 4.30 D; P < 0.001), axial elongation (0.226 ± 0.013 mm vs. 0.183 ± 0.023 mm; P < 0.05), choroidal thinning (-2.01 ± 1.80 µm vs. 1.88 ± 1.27 µm; P < 0.001), and scleral thinning (11.41 ± 3.91 µm vs. 19.72 ± 4.01 µm; P < 0.01) with myopia progression and increased ChBP (52.0% ± 4.1% vs. 59.5% ± 6.3%; P < 0.05). The suppressive effect of BH eye drops was dose-dependent and higher than that of other glaucoma eye drops and alpha1 blockers.

Conclusions

These results demonstrate the potential of BH eye drops in the treatment of myopia and support further investigation of their efficacy in humans. Further studies are needed to determine the mechanism of action and long-term safety of this treatment.

SUBMITTER: Jeong H

PROVIDER: S-EPMC10653257 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Publications

Topical Application of Bunazosin Hydrochloride Suppresses Myopia Progression With an Increase in Choroidal Blood Perfusion.

Jeong Heonuk H Lee Deokho D Jiang Xiaoyan X Negishi Kazuno K Tsubota Kazuo K Kurihara Toshihide T

Investigative ophthalmology & visual science 20231101 14

<h4>Purpose</h4>The incidence of myopia has rapidly increased in recent decades, making it a growing public health concern worldwide. Interventions to suppress the progression of myopia are needed; one suggested strategy is the prevention of choroidal thinning, which can improve choroidal blood perfusion (ChBP). Bunazosin hydrochloride (BH) is an alpha1-adrenergic blocker and commercialized glaucoma eye drop that increases in blood circulation in the eye. In this study, we evaluated the efficacy ...[more]

PMID: 37955611

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Project description:The aim of the present study was to determine and compare the degree and duration of corneal anesthesia following topical application of 0.4% oxybuprocaine hydrochloride ophthalmic solution and 1% ropivacaine hydrochloride treatment in healthy rats. A randomized, blinded, crossover study was conducted on 20 healthy adult Wistar rats, following complete physical and ophthalmological examination. Baseline corneal touch threshold (CTT) was determined in the central corneal area of both eyes with a Cochet-Bonnet aesthesiometer, in mm filament length. Oxybuprocaine was randomly applied to one eye and 0.9% sterile sodium chloride solution was instilled into the contralateral eye. Subsequent CTT measurements were performed in both eyes 5 minutes after topical application and at 5-minute intervals thereafter for 75-minutes in the anesthetized eye. Following a 2-week washout period, this protocol was repeated with ropivacaine. Quantitative data were summarized as mean ± standard deviation, median and inter-quartile range (Q1-Q3). Repeated measures data were analyzed over time and between treatments using Friedman test and Wilcoxon signed-rank test with Bonferroni adjustment (p < 0.05). Baseline CTT values were 60 mm in all eyes. With oxybuprocaine, CTT values decreased significantly for 65 minutes (0-55 mm; p = 0.002) when compared with baseline; the maximal anesthetic effect (no blink response at 5 mm filament length) was maintained for up to 15 minutes (p < 0.0001). With ropivacaine, CTT values were significantly lower than baseline for 30 minutes (0-55 mm; p = 0.002), with a maximal anesthetic effect recorded at 5 minutes in 18 eyes (p < 0.0001). Oxybuprocaine induced a significantly lower CTT than ropivacaine (p = 0.002) from 10 to 65 minutes following topical application. Both anesthetic agents induced significant corneal anesthesia; however, oxybuprocaine provided a greater and longer anesthetic effect, making it more suitable for potentially painful ophthalmologic procedures.

Project description:BackgroundMyopia has emerged as a major public health concern globally, which is tightly associated with scleral extracellular matrix (ECM) remodeling and choroidal vasculopathy. Choroidal vasculopathy has gradually been recognized as a critical trigger of myopic pathology. However, the precise mechanism controlling choroidal vasculopathy remains unclear. Transfer RNA-derived fragments (tRFs) are known as a novel class of small non-coding RNAs that plays important roles in several biological and pathological processes. In this study, we investigated the role of tRF-22-8BWS72092 (tRF-22) in choroidal vasculopathy and myopia progression.MethodsThe tRF-22 expression pattern under myopia-related stresses was detected by qRT-PCR. MTT assays, EdU incorporation assays, Transwell migration assays, and Matrigel assays were conducted to detect the role of tRF-22 in choroidal endothelial cell function in vitro. Isolectin B4 staining and choroidal sprouting assay ex vivo were conducted to detect the role of tRF-22 in choroidal vascular dysfunction in vivo. Immunofluorescent staining, western blot assays and ocular biometric parameters measurement were performed to examine whether altering tRF-22 expression in choroid affects scleral hypoxia and ECM remodeling and myopia progression in vivo. Bioinformatics analysis and luciferase activity assays were conducted to identify the downstream targets of tRF-22. RNA-sequencing combined with m6A-qPCR assays were used to identify the m6A modified targets of METTL3. Gain-of-function and Loss-of-function analysis were performed to reveal the mechanism of tRF-22/METTL3-mediated choroidal vascular dysfunction.ResultsThe results revealed that tRF-22 expression was significantly down-regulated in myopic choroid. tRF-22 overexpression alleviated choroidal vasculopathy and retarded the progression of myopia in vivo. tRF-22 regulated choroidal endothelial cell viability, proliferation, migration, and tube formation ability in vitro. Mechanistically, tRF-22 interacted with METTL3 and blocked m6A methylation of Axin1 and Arid1b mRNA transcripts, which led to increased expression of Axin1 and Arid1b.ConclusionsOur study reveals that the intervention of choroidal vasculopathy via tRF-22-METTL3- Axin1/Arid1b axis is a promising strategy for the treatment of patients with myopic pathology.

Dataset Information

Topical Application of Bunazosin Hydrochloride Suppresses Myopia Progression With an Increase in Choroidal Blood Perfusion.

Purpose

Methods

Results

Conclusions

Publications

Topical Application of Bunazosin Hydrochloride Suppresses Myopia Progression With an Increase in Choroidal Blood Perfusion.

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