Potassium channel and NKCC cotransporter involvement in ocular refractive control mechanisms.

Sheila G Crewther,David P Crewther,Melanie J Murphy

doi:10.1371/journal.pone.0002839

Sheila G Crewther, David P Crewther + Show 1 more

Open Access

PDF Available

https://doi.org/10.1371/journal.pone.0002839

Copy DOI

Export

Save

Cite

Journal: PLoS ONE	Publication Date: Jul 30, 2008
Citations: 24	License type: CC BY 4.0

Affiliation: Swinburne University of Technology, La Trobe University

Abstract
Highlights/Summary
Full-Text PDF
Similar Papers

Abstract

Listen

Myopia affects well over 30% of adult humans globally. However, the underlying physiological mechanism is little understood. This study tested the hypothesis that ocular growth and refractive compensation to optical defocus can be controlled by manipulation of potassium and chloride ion-driven transretinal fluid movements to the choroid. Chicks were raised with +/−10D or zero power optical defocus rendering the focal plane of the eye in front of, behind, or at the level of the retinal photoreceptors respectively. Intravitreal injections of barium chloride, a non-specific inhibitor of potassium channels in the retina and RPE or bumetanide, a selective inhibitor of the sodium-potassium-chloride cotransporter were made, targeting fluid control mechanisms. Comparison of refractive compensation to 5mM Ba2+ and 10−5 M bumetanide compared with control saline injected eyes shows significant change for both positive and negative lens defocus for Ba2+ but significant change only for negative lens defocus with bumetanide ; ; ; ; ; ). Vitreous chamber depths showed a main effect for drug conditions with less depth change in response to defocus shown for Ba2+ relative to Saline, while bumetanide injected eyes showed a trend to increased depth without a significant interaction with applied defocus. The results indicate that both K channels and the NKCC cotransporter play a role in refractive compensation with NKCC blockade showing far more specificity for negative, compared with positive, lens defocus. Probable sites of action relevant to refractive control include the apical retinal pigment epithelium membrane and the photoreceptor/ON bipolar synapse. The similarities between the biometric effects of NKCC inhibition and biometric reports of the blockade of the retinal ON response, suggest a possible common mechanism. The selective inhibition of refractive compensation to negative lens in chick by loop diuretics such as bumetanide suggests that these drugs may be effective in the therapeutic management of human myopia.

Highlights

Myopic eyes in humans and animals are larger in axial dimensions and in volume than emmetropic eyes, while refractively hyperopic eyes are smaller overall than emmetropic eyes of the same age
The experiments reported here demonstrate that both unselective blocking of potassium channels and selective inhibition of the sodium-potassium-chloride symporter can produce dramatic interference with refractive compensation to optically induced blur
As both subretinal [K] and the activity of the NKCC1 symporter of the apical membrane of the retinal pigment epithelium (RPE) are known to affect the shunting of fluid between the retina and the choroid [9,11] these results are consistent with a mechanism of ocular growth and refractive error based on alteration in the rates of ionically controlled transretinal fluid flow, as originally hypothesized by Crewther [6]

Summary

Introduction

Myopic eyes in humans and animals are larger in axial dimensions and in volume than emmetropic eyes, while refractively hyperopic eyes are smaller overall than emmetropic eyes of the same age. In a second experiment, we tested the idea that if negative lens defocus results in myopia and ocular elongation through a reduction in the outflow of fluid across the RPE, intravitreal injection of the diuretic bumetanide would restore RPE fluid flow as evidenced by relative suppression of abnormal vitreal chamber growth and inhibition of myopia.

Results

Conclusion