The Changes of KCNQ5 Expression and Potassium Microenvironment in the Retina of Myopic Guinea Pigs.

Qin Yang,Chang Jun Lan,Bo Zhen Lv,Xuan Liao,Wei Qi Zhong,Qing Qing Tan,Zhi Ming Gu,Gui Mei Zhou,Yu Mei Mao

doi:10.3389/fphys.2021.790580

Abstract

KCNQ5 is suggestively associated with myopia, but its specific role in the myopic process has not been studied further. The aim of this study was to investigate the expression of potassium channel gene KCNQ5 and the changes of K+ microenvironment within the retina of form deprivation myopia (FDM) guinea pigs. A total of 60 guinea pigs were randomly divided into the normal control (NC) group, the self-control (SC) group, and the form-deprivation (FD) group for different treatments. Molecular assays and immunohistochemistry (IHC) were conducted to measure the expression and distribution of KCNQ5-related gene and protein in the retina. We determined the K+ concentration in the retina. In addition, the possible effects of form deprivation on potassium ionic currents and the pharmacological sensitivity of KCNQ5 activator Retigabine and inhibitor XE991 to the M-current in RPE cells were investigated using the patch-clamp technique. As a result, FD eyes exhibited more myopic refraction and longer AL. The mRNA and protein levels of KCNQ5 significantly decreased in the FD eyes, but the K+ concentration increased. In addition, the M-type K+ current [IK(M)] density decreased in FD RPE cells, and were activated or inhibited in a concentration-dependent manner due to the addition of Retigabine or XE991. Overall, KCNQ5 was significantly downregulated in the retina of FD guinea pigs, which may be associated with the increasing K+ concentration, decreasing IK(M) density, and elongating ocular axis. It suggested that KCNQ5 may play a role in the process of myopia, and the intervention of potassium channels may contribute to the prevention and control of myopia.

Highlights

Myopia is the most common refractive error in the world
Given that KCNQ5 encodes a potassium channel found in the retinal pigment epithelium (RPE) and neural retina, it is speculated that it may be involved in the ion transport mechanism underlying myopia
Rat, and bovine have shown that both RPE and neuroretina express KCNQ5 (Zhang et al, 2011; Pattnaik and Hughes, 2012; Zhang and Hughes, 2013; Caminos et al, 2015); Our study further showed that KCNQ5 was mainly distributed in RPE layer, inner and outer segment of photoreceptor, outer plexus layer, inner plexus layer, and ganglion cell layer in the retina of guinea pig by immunohistochemistry detection

Summary

Introduction

Myopia is the most common refractive error in the world. The prevalence of myopia has shown a trend toward younger age and a significant increase, especially with the outbreak of COVID-19 in the past 2 years (Morgan et al, 2017; Wong et al, 2021). Previous studies have shown that refractive development is influenced by environmental, behavioral, and inherited factors The association of KCNQ5 with refractive error and myopia has been identified by genome wide association study (Kiefer et al, 2013; Verhoeven et al, 2013; Li et al, 2021) and further verified by our previous study (Liao et al, 2017). Previous studies have shown that myopia may be related to dysregulation of potassium ion homeostasis in the retina and ciliary muscle (Crewther et al, 2006; Wu et al, 2020). Given that KCNQ5 encodes a potassium channel found in the RPE and neural retina, it is speculated that it may be involved in the ion transport mechanism underlying myopia

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