Intravitreal brimonidine inhibits form-deprivation myopia in guinea pigs

Abstract

Background 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. Methods 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. Results 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. Conclusions 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.

Comparison of the accuracy of axial length measurement by different imaging methods in Sprague Dawley rats

“…Therefore, A-scan is more suitable for the measurement of AL in small animals. In fact, in most studies of small rodent myopia models, AL was measured by A-scan Yang et al, 2021;Yu et al, 2021). This is the reason why two kinds of A-scan were selected to measure the AL of rats in this study.…”

Brimonidine as a possible treatment for myopia

“…Carr et al found that brimonidine at 20nmol/20 µ L (approximately 0.442ug/ µ L) and 200nmol/20 µ L (approximately 4.422ug/ µ L) of injected intravitreally was effective in slowing the progression of form-deprivation myopia in chicks [ 5 ]. Our groups previously reported similar results, in that that intravitreal injection of 4 µ g/ µ L brimonidine was effective in slowing the progression of form-deprivation myopia in guinea pigs [ 8 ]. The results of the present experiment, specifically that 4ug/ µ L intravitreally is effective, are generally consistent with the results of these two studies.…”

“…Based on the above findings, our laboratory discovered that intravitreal injection at 4 µg/µL was effective in slowing the progression of form-deprivation myopia in guinea pigs [ 8 ], while the same concentration of brimonidine administered through eye drops and subconjunctival injections proved ineffective. This finding encourages further investigation, as different drug delivery methods affect therapeutic efficacy by influencing drug utilisation.…”

Lowering Intraocular Pressure: A Potential Approach for Controlling High Myopia Progression

“… 28 In addition, both brimonidine eye drops and intravitreal injections were reported to be effective in inhibiting progressing myopia, mainly through slowing AL elongation. 29 , 30 …”