Disrupted potassium ion homeostasis in ciliary muscle in negative lens-induced myopia in Guinea pigs.

Myopia is a main cause of preventable or treatable visual impairment, it has become a major public health issue due to its increasingly high prevalence worldwide. Currently, it is confirmed that the development of myopia is associated with the disorders of accommodation. As a dominant factor for accommodation, ciliary muscle contraction/relaxation can regulate the physiological state of the lens and play a crucial role in the development of myopia. To investigate the relationship between myopia and ciliary muscle, the guinea pigs were randomly divided into a normal control (NC) group and a negative lens-induced myopia (LIM) group, and the animals in each group were further randomly assigned into 2-week (n = 18) and 4-week (n = 21) subgroups in accordance with the duration of myopic induction of 2 and 4 weeks, respectively. In the present study, right eyes of the animals in LIM group were covered with -6.0 D lenses to induce myopia. Next, we performed the haematoxylin and eosin (H&E) staining to observe the pathological change of ciliary muscle, determined the contents of adenosine triphosphate (ATP) and lactate acid (LA), and measured the Na+/K+-ATPase expression and activity in ciliary muscles in both NC and LIM groups. Moreover, we also analyzed the potassium ion (K+) flux in ciliary muscles from 4-week NC and LIM guinea pigs. As a result, we found that the arrangements of ciliary muscles in LIM guinea pigs were broken, dissolved or disorganized; the content of ATP decreased, whereas the content of LA increased in ciliary muscles from LIM guinea pigs. Monitoring of K+ flux in ciliary muscles from LIM guinea pigs demonstrated myopia-triggered K+ influx. Moreover, we also noted a decreased expression of Na+/K+-ATPase (Atp1a1) at both mRNA and protein levels and reduced activity in ciliary muscles from LIM guinea pigs. Overall, our results will facilitate the understanding of the mechanism associated with inhibitory Na+/K+-ATPase in lens-induced myopia and which consequently lead to the disorder of microenvironment within ciliary muscles from LIM guinea pigs, paving the way for a promising adjuvant approach in treating myopia in clinical practice.

Alternation of Resting-State Functional Connectivity Between Visual Cortex and Hypothalamus in Guinea Pigs With Experimental Glucocorticoid Enhanced Myopia After the Treatment of Electroacupuncture.

Excessive glucocorticoids (GC) may lead to the aggravation of several basic diseases including myopia, due to plasma hormone imbalances associated with the hypothalamic-pituitary-adrenal axis (HPAA). Electroacupuncture (EA) is an effective therapeutic method to treat many diseases, although it remains unclear whether EA at acupoints on the foot or back would be effective in treating eye diseases. It was recently found that visual cortex activity for responses to visual stimuli with spatial frequency and resting-state functional connectivity (FC) between the supramarginal gyrus and rostrolateral prefrontal cortex was significantly reduced in patients with high myopia. The present study aims to investigate the role of the alternation of resting-state FC among the bilateral visual cortex and hypothalamus in exerting anti-myopia effects of EA in GC-enhanced lens-induced myopic (LIM) guinea pigs such that the mechanisms of EA to treat GC-enhanced myopia at Shenshu (BL23) acupoints can be probed. To confirm the effects of EA, ocular parameters including axial length and GC-associated physiological parameters such as animal appearance, behavior, bodyweight, and levels of four HPAA-associated plasma hormones [free triiodothyronine (FT3), free thyroxine (FT4), estradiol (E2), and testosterone (T)] were also collected. Increased resting-state FC between the left and right visual cortex was detected in GC-enhanced lens-induced myopic guinea pigs with EA at BL23 acupoints (LIM+GC+EA) guinea pigs compared to GC-enhanced lens-induced myopic guinea pigs with EA at sham acupoints (LIM+GC+Sham) guinea pigs, as well as suppressed myopia and recovery of symptoms initially caused by overdose of GC. Recovered symptoms included improved animal appearance, behavior, bodyweight, and HPAA-associated plasma hormone levels were observed after 4 weeks of EA treatment. In contrast, the LIM+GC+Sham group showed decreased FC with elongation of axial length for myopization as compared to the control group and LIM group and exhibited a deterioration in physiological parameters including reduced body weight and balance disruption in the four measured HPAA-associated plasma hormones. Our findings suggest that EA could effectively treat GC-enhanced myopia by increasing resting-state FC between the left and right visual cortices, which may be pivotal to further understanding the application and mechanisms of EA in treating GC-enhanced myopia.