Morphological ciliary muscle changes associated with form deprivation-induced myopia
Introduction
The ciliary muscle's link to myopia development has long been suspected. Historically, near work (cumulative accommodative effort) was considered a primary risk factor for myopia development (Zylbermann et al., 1993). However, more recently, the relationship between the risk of myopia onset and near work has been questioned (Huang et al., 2015; Ip et al., 2008; Saw et al., 2006; Zadnik et al., 2015). While near work has lost some favor, the accommodative system is still relevant to myopia development because myopic individuals have increased accommodative lags (Gwiazda et al., 2005; Mutti et al., 2006), higher AC/A ratios (Gwiazda et al., 2005; Mutti et al., 2000), and thicker ciliary muscles/bodies (Bailey et al., 2008; Oliveira et al., 2005; Pucker et al., 2013). Subsequently, these associations have led to the hypothesis that ciliary muscle thickening may play a role in producing the relatively less oblate ocular shape found in myopic eyes, specifically that ciliary muscle thickening may cause equatorial eye restriction resulting in axial elongation without proportional equatorial expansion (Atchison et al., 2005, 2006; Mutti et al., 2007).
A less oblate ocular shape in humans is also associated with a more hyperopic relative peripheral refraction (Atchison et al., 2005, 2006; Mutti et al., 2007), a feature that is currently believed to be a key regulator of myopia development (Aller and Wildsoet, 2013; Anstice and Phillips, 2011; Liu and Wildsoet, 2012; Sankaridurg et al., 2011; Smith et al., 2009; Walline et al., 2013). Foveal visual cues may be important for regulating refractive error development, but the peripheral retina has been shown to guide eye growth without input from the fovea in animal models (Smith et al., 2009). Smith et al. demonstrated that if one ablates a rhesus monkey's fovea, peripheral visual stimuli (form deprivation and minus lenses) are still able to induce axial elongation and myopic refractive error at the fovea (Smith et al., 2007, 2009). The success of treating human peripheral hyperopic defocus with orthokeratology and center-distance bifocal contact lenses reinforces the peripheral visual defocus theory (Aller and Wildsoet, 2013; Anstice and Phillips, 2011; Cho et al., 2005; Sankaridurg et al., 2011; Walline et al., 2009, 2013). Yet the myopia community currently lacks a mechanistic understanding of how a less oblate myopic eye shape is created.
The guinea pig is an attractive animal model for investigating this mechanism because: 1) guinea pigs reach adulthood within about 90 days of life, 2) guinea pigs have the ability to accommodate, 3) untreated guinea pig ciliary muscle volume increases 2.5 fold during their first 90 days of life, and 4) guinea pigs have prominent longitudinal ciliary muscle fibers (region of muscle associated with human myopia) (Howlett and McFadden, 2006, 2007; 2009; Ostrin et al., 2014; Pucker et al., 2014, 2015). However, it is unclear whether induced myopia alters the ciliary muscle growth pattern of guinea pigs, which is a first step toward understanding whether there may be a causal relationship between ciliary thickness and myopia development. Therefore, the purpose of the study was to investigate whether form deprivation-induced myopia in one or more strains of guinea pig causes thickening of the ciliary muscle as seen in human myopia.
Section snippets
Animals
This study utilized Strain 13 guinea pigs (n = 14; Cavia porcellus) that were obtained from the United States Army Medical Research Institute of Infectious Diseases (Fort Detrick, MD) and a guinea pig strain with unknown origins (Cincinnati strain; n = 25) that is currently being maintained by Cincinnati Children's Hospital (Cincinnati, OH). Commercially available guinea pigs from Elm Hill Labs (Chelmsford, MA) were excluded because they are known to be resistant to myopia induction (Jiang et
Biometric measurements
All guinea pigs were able to successfully wear the form-deprivation hoods. The lenses stayed on all hoods, though four of guinea pigs had their hood fall off between one and two times. Hood removal did not result in a discernible link to being responsive to the treatment. There was no substantial variation in the percentages of animals in each response group between the two strains. The Cincinnati guinea pigs were between 50% and 73% of the animals in each of the four response groups, similar
Discussion
An association between thicker human ciliary bodies/muscles and myopic refractive errors in children and adults is well established in the literature, yet the mechanism leading to a thicker ciliary body/muscle is currently unknown, motivating the need to study ciliary muscle development in animal models (Bailey et al., 2008; Oliveira et al., 2005; Pucker et al., 2013). The purpose of the study was to investigate whether form deprivation-induced myopia in one or more strains of guinea pig causes
Acknowledgements
The authors thank the National Eye Institute (K08EY023264; P30EY003039) and the University of Alabama at Birmingham (Investment Pool for Action Funds) for financial and equipment support during this experiment. The authors also thank the United States Army Medical Research Institute of Infectious Diseases and Cincinnati Children's Hospital for providing the guinea pigs strains used in this study. This work was completed in partial fulfillment of ADP's PhD dissertation.
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