Optometry and Vision Sciences - Research Publications
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ItemExpression of muscarinic receptor subtypes in tree shrew ocular tissues and their regulation during the development of myopia(MOLECULAR VISION, 2009-03-02)PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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ItemNo Preview AvailableThe Effect of Daily Transient+4 D Positive Lens Wear on the Inhibition of Myopia in the Tree Shrew(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2012-03)PURPOSE: Negative-lens-induced defocus causes accelerated ocular elongation and myopia, whereas positive-lens-induced defocus produces reduced ocular elongation and hyperopia. Short durations of positive lens wear result in markedly stronger temporal effects than do short periods of negative lens wear in the chick model of refractive development. In mammalian and nonhuman primate models, there have been equivocal results in inhibiting myopia by short periods of positive lens wear when compared with data from the chick model. The purpose of the present study was an evaluation of full-time -9.5 D negative lens wear interrupted by short periods of daily +4 D positive lens wear in preventing experimental myopia in the tree shrew. METHODS: One treatment group wore negative lenses (-9.5 D) binocularly for 23 hours a day (10 hours of which were spent in total darkness), interrupted by 1 hour of wearing positive lenses (+4 D) binocularly for 12 days. Another group of animals wore negative lenses (-9.5 D) binocularly for 23 hours a day, interrupted by two 30-minute periods of positive lens (+4 D) wear daily, again for 12 days. The animals were raised on a 14-hour/10-hour light-dark cycle. Animals wearing -9.5 D lenses binocularly, interrupted by 0-powered lenses for either 1 hour or two 30-minute periods daily for 12 days, acted as controls. RESULTS: Continuous wear of -9.5 D lenses binocularly induced a -10.8 D myopic shift in refraction. Full-time wear of -9.5 D lenses binocularly, interrupted by 1 hour of 0-power lens wear binocularly, caused a myopic shift of 3.6 D over 12 days, whereas wearing -9.5 D lenses, interrupted by 1 hour every day of +4.0 D lens wear binocularly, whether it was continuous or divided into two 30-minute periods, caused a myopic shift of only 0.7 D over 12 days. CONCLUSIONS: Daily intermittent +4 D positive lens wear effectively inhibits experimentally induced myopia and may prove a viable approach for preventing myopia progression in children.
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ItemNo Preview AvailableEyes in Various Species Can Shorten to Compensate for Myopic Defocus(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2013-04)PURPOSE: We demonstrated that eyes of young animals of various species (chick, tree shrew, marmoset, and rhesus macaque) can shorten in the axial dimension in response to myopic defocus. METHODS: Chicks wore positive or negative lenses over one eye for 3 days. Tree shrews were measured during recovery from induced myopia after 5 days of monocular deprivation for 1 to 9 days. Marmosets were measured during recovery from induced myopia after monocular deprivation, or wearing negative lenses over one or both eyes, or from wearing positive lenses over one or both eyes. Rhesus macaques were measured after recovery from induced myopia after monocular deprivation, or wearing negative lenses over one or both eyes. Axial length was measured with ultrasound biometry in all species. RESULTS: Tree shrew eyes showed a strong trend to shorten axially to compensate for myopic defocus. Of 34 eyes that recovered from deprivation-induced myopia for various durations, 30 eyes (88%) shortened, whereas only 7 fellow eyes shortened. In chicks, eyes wearing positive lenses reduced their rate of ocular elongation by two-thirds, including 38.5% of eyes in which the axial length became shorter than before. Evidence of axial shortening in rhesus macaque (40%) and marmoset (6%) eyes also occurred when exposed to myopic defocus, although much less frequently than that in eyes of tree shrews. The axial shortening was caused mostly by the reduction in vitreous chamber depth. CONCLUSIONS: Eyes of chick, tree shrew, marmoset, and rhesus macaque can shorten axially when presented with myopic defocus, whether the myopic defocus is created by wearing positive lenses, or is the result of axial elongation of the eye produced by prior negative lens wear or deprivation. This eye shortening facilitates compensation for the imposed myopia. Implications for human myopia control are significant.
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ItemNo Preview AvailableMuscarinic Antagonist Control of Myopia: Evidence for M4 and M1 Receptor-Based Pathways in the Inhibition of Experimentally-Induced Axial Myopia in the Tree Shrew(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2012-08)PURPOSE: The broadband muscarinic antagonist atropine is effective in stopping the progression of myopia in animals and humans. The partially selective M(1)/M(4) antagonist pirenzepine also slows progression of myopia, although not as effectively as atropine. Due to the supra maximal doses utilized in these studies, it is unclear if this antimyopia effect occurs through a receptoral-based mechanism, and if so, which receptors are involved. Studies in chicks indicate the involvement of the M(4) muscarinic receptor. The current study investigated the effect of the highly selective muscarinic antagonists Muscarinic Toxin 3 (MT3) (M(4) selective) and Muscarinic Toxin 7 (MT7) (M(1) selective) on experimental myopia in a mammalian model. METHODS: Tree shrews (n = 23) underwent daily intravitreal injections of MT3, MT7, or vehicle (phosphate buffered saline) for five days in the treated eye, combined with deprivation of vision with a translucent occluder (MD). The contralateral eye was unocccluded and underwent intravitreal injections of vehicle for the same period. Two additional groups (n = 10) underwent daily intravitreal injections of MT7 or vehicle for 10 days in the treated eye combined with negative lens (-9.5 diopter [D]) defocus (LIM). The control eye was injected with saline and wore a plano lens. RESULTS: Both MT3 and MT7 treatment reduced the development of deprivation-induced myopia (treated-control eye [T-C]; vehicle-MD; -4.3 ± 0.6 D versus MT3-MD; -0.7 ± 0.2 D and MT7-MD; -0.7 ± 0.4 D; P < 0.001). MT7 treatment was effective at inhibiting lens-induced myopia (T-C; vehicle-LIM; -4.6 ± 0.5 D versus MT7-LIM; 0.2 ± 0.2 D; P < 0.05). CONCLUSIONS: The findings demonstrate that inhibition of form-deprivation myopia by muscarinic antagonists involves both M(4) and M(1) muscarinic receptor signaling pathways in mammals.
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