The use of ocular hypotensive drugs has been reported to attenuate myopia progression. This study explores whether brimonidine can slow myopia progression in the guinea pig form-deprivation (FD) model. Three-week-old pigmented male guinea pigs (Cavia porcellus) underwent monocular FD and were treated with 3 different methods of brimonidine administration (eye drops, subconjunctival or intravitreal injections). Four different concentrations of brimonidine were tested for intravitreal injection (2 μg/μL, 4 μg/μL, 20 μg/μL, 40 μg/μL). All treatments continued for a period of 21 days. Tonometry, retinoscopy, and A-scan ultrasonography were used to monitor intraocular pressure (IOP), refractive error and axial length (AL), respectively. On day 21, guinea pigs were sacrificed for RNA sequencing (RNA-seq) to screen for associated transcriptomic changes. The myopia model was successfully established in FD animals (control eye vs. FD eye, respectively: refraction at day 20, 0.97 ± 0.18 D vs. − 0.13 ± 0.38 D, F = 6.921, P = 0.02; AL difference between day 0 and day 21, 0.29 ± 0.04 mm vs. 0.45 ± 0.03 mm, F = 11.655, P = 0.004). Among the 3 different brimonidine administration methods, intravitreal injection was the most effective in slowing myopia progression, and 4 μg/μL was the most effective among the four different concentrations of brimonidine intravitreal injection tested. The AL and the refraction of the brimonidine intravitreal injection group was significantly shorter or more hyperopic than those of other 2 groups. Four μg/μL produced the smallest difference in AL and spherical equivalent difference values. FD treatment significantly increased the IOP. IOP was significantly lower at 1 day after intravitreal injections which was the lowest in FD eye of intravitreal injection of brimonidine. At day 21, gene expression analyses using RNA-seq showed upregulation of Col1a1 and Mmp2 expression levels by intravitreal brimonidine. Among the 3 different administration methods, intravitreal injection of brimonidine was the most effective in slowing myopia progression in the FD guinea pig model. Intravitreal brimonidine at 4 μg/μL significantly reduced the development of FD myopia in guinea pigs. Expression levels of the Col1a1 and Mmp2 genes were significantly increased in the retinal tissues of the FD-Inj-Br group.

中文翻译：

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玻璃体内注射溴莫尼定抑制豚鼠形式剥夺性近视

据报道，降眼压药物的使用可以减轻近视的进展。本研究探讨溴莫尼定是否可以减缓豚鼠形式剥夺 (FD) 模型中的近视进展。三周大的有色雄性豚鼠 (Cavia porcellus) 接受了单眼 FD，并用 3 种不同的溴莫尼定给药方法（滴眼液、结膜下或玻璃体内注射）进行治疗。测试了四种不同浓度的溴莫尼定用于玻璃体内注射（2 μg/μL、4 μg/μL、20 μg/μL、40 μg/μL）。所有治疗持续21天。眼压计、检影和 A 型超声分别用于监测眼压 (IOP)、屈光不正和轴向长度 (AL)。在第 21 天，处死豚鼠进行 RNA 测序 (RNA-seq)，以筛选相关的转录组变化。在 FD 动物中成功建立近视模型（对照眼与 FD 眼分别为：第 20 天的屈光度，0.97 ± 0.18 D vs. − 0.13 ± 0.38 D，F = 6.921，P = 0.02；第 0 天和第 0 天之间的 AL 差异第 21 天，0.29 ± 0.04 毫米与 0.45 ± 0.03 毫米，F = 11.655，P = 0.004）。在 3 种不同的溴莫尼定给药方法中，玻璃体内注射对减缓近视进展最有效，4 μg/μL 在所测试的四种不同浓度的溴莫尼定玻璃体内注射中最有效。溴莫尼定玻璃体内注射组的 AL 和屈光度明显短于其他 2 组或更远视。4 μg/μL 在 AL 和球面等效差值方面产生的差异最小。FD 治疗显着增加了 IOP。玻璃体内注射后1天IOP显着降低，这是玻璃体内注射溴莫尼定的FD眼中最低的。在第 21 天，使用 RNA-seq 的基因表达分析显示玻璃体内溴莫尼定上调 Col1a1 和 Mmp2 的表达水平。在 3 种不同的给药方法中，玻璃体内注射溴莫尼定在 FD 豚鼠模型中减缓近视进展最有效。4 μg/μL 的玻璃体内注射溴莫尼定显着降低了豚鼠 FD 近视的发展。Col1a1 和 Mmp2 基因的表达水平在 FD-Inj-Br 组的视网膜组织中显着增加。使用 RNA-seq 的基因表达分析显示玻璃体内溴莫尼定上调 Col1a1 和 Mmp2 表达水平。在 3 种不同的给药方法中，玻璃体内注射溴莫尼定在 FD 豚鼠模型中减缓近视进展最有效。4 μg/μL 的玻璃体内注射溴莫尼定显着降低了豚鼠 FD 近视的发展。Col1a1 和 Mmp2 基因的表达水平在 FD-Inj-Br 组的视网膜组织中显着增加。使用 RNA-seq 的基因表达分析显示玻璃体内溴莫尼定上调 Col1a1 和 Mmp2 表达水平。在 3 种不同的给药方法中，玻璃体内注射溴莫尼定在 FD 豚鼠模型中减缓近视进展最有效。4 μg/μL 的玻璃体内注射溴莫尼定显着降低了豚鼠 FD 近视的发展。Col1a1 和 Mmp2 基因的表达水平在 FD-Inj-Br 组的视网膜组织中显着增加。