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Updated: Aug 9, 2026
Inducement and Evaluation of a Murine Model of Experimental Myopia
Published on: January 22, 2019
[Effect of pirenzepine on form deprivation myopia in chicks and its possible mechanism]
Shu-zhen Dai1, Jun-wen Zeng, Li-ya Wang
1Ophthalmic Institute of Henan Province, Zhengzhou 450003, China.
Objective:
To observe the effect of M1-selective muscarinic antagonist, pirenzepine, on form deprivation myopia and investigate the expression of MMP-2 and its inhibitor TIMP-2 in the fibrous sclera in order to better understand the mechanism by which pirenzepine inhibits myopia.
Methods:
40 chicks after birth one day were divided into 4 groups randomly: I. Control group; II. Form deprivation group; III. Vehicle application group; IV. Pirenzepine injected group. Form deprivation myopia was established in right eyes of group II, III, IV by placement of a translucent occluder. The deprived eyes of group III and IV received daily subconjunctival administration of vehicle PBS and pirenzepine respectively. Optical measures such as refraction, axial length, equatorial diameter were made at the end of the experiment. Total RNA and protein were extracted from the posterior fibrous sclera chicks. The expression of MMP-2 and TIMP-2 mRNA and protein were investigated with RT-PCR and Western blot analysis respectively.
Results:
Refraction status, axial length, equatorial diameter of the eyes in pirenzepine injected group were significantly lower when compared with form deprivation group (P < 0.01), but the parameters were higher when compared with normal control group therefore relatively myopic changes were detected. There were no significant difference between drug control and pirenzepine injected group when optical measures and the expression of MMP-2, TIMP-2 were concerned (P > 0.05). The expressions (mRNA and protein) of both MMP-2 and TIMP-2 were significantly different in form deprivation group when compared with normal control group (MMP-2 mRNA increased by 143.51%, P < 0.01; protein increased by 114.60%, P < 0.01; TIMP-2 mRNA decreased by 55.05%, P < 0.01; protein decreased by 53.73%, P < 0.01). In pirenzepine injected group the relative expression of MMP-2 mRNA and protein were decreased obviously by 41.95% (P < 0.01) and by 36.16% (P < 0.01), while TIMP-2 mRNA and protein expression was increased significantly by 72.46% (P < 0.01) and by 53.05% (P < 0.01) respectively compared with the form deprived group.
Conclusion:
Subconjunctivally administration of the M1 selective muscarinic antagonist, pirenzepine, partly prevents or restrains form deprivation induced myopia. It may exert its inhibitory effect by modulating the expression of MMP-2 and TIMP-2 in fibrous sclera.
Insights
Pirenzepine, an M1-selective muscarinic antagonist, partly prevents form deprivation myopia in chicks. This myopia treatment may work by altering matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) expression in the sclera.
Area of Science:
- Ophthalmology
- Pharmacology
- Molecular Biology
Context:
- Form deprivation myopia is a significant concern in pediatric eye care.
- The precise molecular mechanisms underlying myopia progression remain under investigation.
- M1-selective muscarinic antagonists are being explored for their potential therapeutic effects on myopia.
Purpose:
- To evaluate the efficacy of pirenzepine, an M1-selective muscarinic antagonist, in preventing form deprivation myopia.
- To investigate the impact of pirenzepine on the expression of matrix metalloproteinase-2 (MMP-2) and its inhibitor, tissue inhibitor of metalloproteinase-2 (TIMP-2), in the fibrous sclera.
- To elucidate the potential mechanism of pirenzepine's anti-myopic effects.
Summary:
- Subconjunctival administration of pirenzepine in chicks partially inhibited form deprivation-induced myopia, as evidenced by reduced axial length and refractive error.
- Form deprivation significantly altered MMP-2 and TIMP-2 expression in the sclera, with increased MMP-2 and decreased TIMP-2.
- Pirenzepine treatment reversed these changes, decreasing MMP-2 and increasing TIMP-2 expression.
Impact:
- Pirenzepine demonstrates potential as a therapeutic agent for myopia.
- Modulation of MMP-2 and TIMP-2 in the sclera represents a key mechanism in pirenzepine's anti-myopic action.
- This study provides insights into the molecular basis of myopia and potential pharmacological interventions.
