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Inducement and Evaluation of a Murine Model of Experimental Myopia
Published on: January 22, 2019
Myopia control in Mendelian forms of myopia
Emilie van der Sande1,2,3, Jan Roelof Polling1,2,4, J Willem L Tideman1,2,5
1Department Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands.
Insights
High-dose atropine effectively reduced axial length progression in children with Mendelian myopia and in mice with genetic myopia. This treatment shows promise for managing myopia, even in cases with a strong genetic basis.
Area of Science:
- Ophthalmology
- Genetics
- Pharmacology
Background:
- Myopia is a common refractive error, with Mendelian forms caused by single gene mutations.
- Understanding the genetic basis of myopia is crucial for developing targeted treatments.
- High-dose atropine has shown potential in slowing myopia progression.
Purpose of the Study:
- To evaluate the efficacy of high-dose atropine in reducing eye growth in children with Mendelian myopia.
- To investigate the effect of high-dose atropine on myopia progression in a mouse model of genetic myopia.
Main Methods:
- Children with and without Mendelian myopia were treated with high-dose atropine, and axial length (AL) progression was compared to population data.
- A mouse model (Lrp2 knockout) of Mendelian myopia was treated with atropine, and ocular biometry was assessed.
- Retinal dopamine and DOPAC levels were measured in mice post-treatment.
Main Results:
- Atropine reduced AL progression by 27% in children with Mendelian myopia and 23% in non-Mendelian myopes compared to untreated controls.
- High-dose atropine significantly reduced AL growth in both knockout and control mice.
- Retinal dopamine and DOPAC levels showed non-significant increases after atropine treatment.
Conclusions:
- High-dose atropine demonstrated comparable efficacy in reducing axial length progression in children with and without Mendelian myopia.
- Atropine effectively reduced myopia progression in a mouse model of severe Mendelian myopia.
- These findings suggest atropine's potential to manage myopia progression, irrespective of a strong monogenic cause.
Purpose:
To study the effectiveness of high-dose atropine for reducing eye growth in Mendelian myopia in children and mice.
Methods:
We studied the effect of high-dose atropine in children with progressive myopia with and without a monogenetic cause. Children were matched for age and axial length (AL) in their first year of treatment. We considered annual AL progression rate as the outcome and compared rates with percentile charts of an untreated general population. We treated C57BL/6J mice featuring the myopic phenotype of Donnai-Barrow syndrome by selective inactivation of Lrp2 knock out (KO) and control mice (CTRL) daily with 1% atropine in the left eye and saline in the right eye, from postnatal days 30-56. Ocular biometry was measured using spectral-domain optical coherence tomography. Retinal dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were measured using high-performance liquid chromatography.
Results:
Children with a Mendelian form of myopia had average baseline spherical equivalent (SE) -7.6 ± 2.5D and AL 25.8 ± 0.3 mm; children with non-Mendelian myopia had average SE -7.3 ± 2.9 D and AL 25.6 ± 0.9 mm. During atropine treatment, the annual AL progression rate was 0.37 ± 0.08 and 0.39 ± 0.05 mm in the Mendelian myopes and non-Mendelian myopes, respectively. Compared with progression rates of untreated general population (0.47 mm/year), atropine reduced AL progression with 27% in Mendelian myopes and 23% in non-Mendelian myopes. Atropine significantly reduced AL growth in both KO and CTRL mice (male, KO: -40 ± 15; CTRL: -42 ± 10; female, KO: -53 ± 15; CTRL: -62 ± 3 μm). The DA and DOPAC levels 2 and 24 h after atropine treatment were slightly, albeit non-significantly, elevated.
Conclusions:
High-dose atropine had the same effect on AL in high myopic children with and without a known monogenetic cause. In mice featuring a severe form of Mendelian myopia, atropine reduced AL progression. This suggests that atropine can reduce myopia progression even in the presence of a strong monogenic driver.
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