Expression of muscarinic receptor subtypes in tree shrew ocular tissues and their regulation during the development of myopia

Muscarinic receptors are known to regulate several important physiologic processes in the eye. Antagonists to these receptors such as atropine and pirenzepine are effective at stopping the excessive ocular growth that results in myopia. However, their site of action is unknown. This study details ocular muscarinic subtype expression within a well documented model of eye growth and investigates their expression during early stages of myopia induction. Total RNA was isolated from tree shrew corneal, iris/ciliary body, retinal, choroidal, and scleral tissue samples and was reverse transcribed. Using tree shrew-specific primers to the five muscarinic acetylcholine receptor subtypes (CHRM1-CHRM5), products were amplified using polymerase chain reaction (PCR) and their identity confirmed using automated sequencing. The expression of the receptor proteins (M1-M5) were also explored in the retina, choroid, and sclera using immunohistochemistry. Myopia was induced in the tree shrew for one or five days using monocular deprivation of pattern vision, and the expression of the receptor subtypes was assessed in the retina, choroid, and sclera using real-time PCR. All five muscarinic receptor subtypes were expressed in the iris/ciliary body, retina, choroid, and sclera while gene products corresponding to CHRM1, CHRM3, CHRM4, and CHRM5 were present in the corneal samples. The gene expression data were confirmed by immunohistochemistry with the M1-M5 proteins detected in the retina, choroid, and sclera. After one or five days of myopia development, muscarinic receptor gene expression remained unaltered in the retinal, choroidal, and scleral tissue samples. This study provides a comprehensive profile of muscarinic receptor gene and protein expression in tree shrew ocular tissues with all receptor subtypes found in tissues implicated in the control of eye growth. Despite the efficacy of muscarinic antagonists at inhibiting myopia development, the genes of the muscarinic receptor subtypes are neither regulated early in myopia (before measurable axial elongation) nor after significant structural change

A Review of Myopia Control with Atropine

Myopia is a global public health issue with a worldwide prevalence of ∼30% and is estimated to rise to 50% by 2050. In addition to the burden associated with routine management of the condition, high myopia predisposes the eye to sight-threatening complications such as myopic maculopathy and glaucoma in adult life. Controlling onset and progression of myopia at a young age can reduce the risk of morbidity associated with high myopia. Progression of myopia can be slowed with various optical, environmental, and pharmaceutical strategies, of which atropine has proven to be the most effective. High-dose atropine (0.5%-1%) is the most effective, but it has significant trade-offs with respect to rebound of myopia on discontinuation and side effects such as photophobia and difficulty with near work (decreased accommodation). Low doses of atropine have been trialed and show a dose-dependent efficacy. However, its mode of action on the ocular tissues leading to slowing eye growth remains unclear and multiple mechanisms and sites in the eye have been postulated to play a role. This review summarizes the role of atropine in controlling myopia and the mechanisms studied to date.</p