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Spatial and temporal dissociation of AQP4 and Kir4.1 expression during induction of refractive errors.

Goodyear MJ, Crewther SG, Murphy MJ, Giummarra L, Hazi A, Junghans BM, Crewther DP - Mol. Vis. (2010)

Bottom Line: Positive lens-wearing eyes showed reduced ocular growth compared to normal controls and developed a hyperopic refraction.Kir4.1 channel upregulation in the inner plexiform layer was only found on day 4 of positive lens wear during the development of refractive hyperopia.Increased AQP4 expression in the nerve fiber layer is suggested to contribute to the rapid axial elongation and movement of fluid into the vitreous cavity in the presence of minus lenses; whereas, upregulation of Kir4.1 channels appears to play a role in limiting axial elongation in the presence of plus lenses.

View Article: PubMed Central - PubMed

Affiliation: School of Psychological Sciences, La Trobe University, Melbourne, Victoria, Australia.

ABSTRACT

Purpose: Spatial co-localization of aquaporin water channels (AQP4) and inwardly rectifying potassium ion channels (Kir4.1) on the endfeet regions of glial cells has been suggested as the basis of functionally interrelated mechanisms of osmoregulation in brain edema. The aim of this study was to investigate the spatial and temporal changes in the expression of AQP4 and Kir4.1 channels in an avascular retina during the first week of the optical induction of refractive errors.

Methods: Three-day-old hatchling chicks were randomly assigned to three groups and either did not wear lenses or were monocularly goggled with +/-10D lenses for varying times up to 7 days before biometric assessment. Retinal tissue was prepared either for western blot analysis to show the presence of the AQP4 and Kir4.1 protein in the chick retina or for immunolocalization using AQP4 and Kir4.1 antibodies to determine the regional distribution and intensity of labeling during the induction of refractive errors.

Results: As expected, ultrasonography demonstrated that all eyes showed rapid elongation post hatching. Negative lens-wearing eyes elongated faster than fellow eyes or normal non goggled eyes and became progressively more myopic with time post lensing. Positive lens-wearing eyes showed reduced ocular growth compared to normal controls and developed a hyperopic refraction. Quantitative immunohistochemistry revealed the upregulation of AQP4 channel expression on Müller cells in the retinal nerve fiber layer during the first 2 days of negative lens wear. Kir4.1 channel upregulation in the inner plexiform layer was only found on day 4 of positive lens wear during the development of refractive hyperopia.

Conclusions: These results indicate that the expression of AQP4 and Kir4.1 channels on Müller cells is associated with the changes in ocular volume seen during the induction of refractive errors. However, the sites of greatest expression and the temporal pattern of the upregulation of AQP4 and Kir4.1 were dissimilar, indicating a dissociation of AQP4 and Kir4.1 function during refractive error development. Increased AQP4 expression in the nerve fiber layer is suggested to contribute to the rapid axial elongation and movement of fluid into the vitreous cavity in the presence of minus lenses; whereas, upregulation of Kir4.1 channels appears to play a role in limiting axial elongation in the presence of plus lenses.

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Comparison of the spatial and temporal distribution of AQP4 and Kir4.1 channel expression during the induction of refractive compensation to optical defocus (using pixel intensity analysis of stained sections). Blue stars indicate significant differences between the lens groups and/or control (No Lens) group (*p<0.05). Figures show the ratio mean luminance levels from the right eye (experimental eye) compared to the fellow left eye. A is the mean ratio luminance levels for AQP4 in the nerve fiber layer (NFL), B is the mean ratio luminance levels for Kir4.1 in the inner plexiform layer (IPL), C is the mean ratio luminance levels for Kir4.1 in sublamina A in the IPL, and D is the mean ratio luminance levels for Kir4.1 in sublamina B in the IPL.
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f5: Comparison of the spatial and temporal distribution of AQP4 and Kir4.1 channel expression during the induction of refractive compensation to optical defocus (using pixel intensity analysis of stained sections). Blue stars indicate significant differences between the lens groups and/or control (No Lens) group (*p<0.05). Figures show the ratio mean luminance levels from the right eye (experimental eye) compared to the fellow left eye. A is the mean ratio luminance levels for AQP4 in the nerve fiber layer (NFL), B is the mean ratio luminance levels for Kir4.1 in the inner plexiform layer (IPL), C is the mean ratio luminance levels for Kir4.1 in sublamina A in the IPL, and D is the mean ratio luminance levels for Kir4.1 in sublamina B in the IPL.

Mentions: A similar regional distribution of AQP4 labeling was found between myopic, hyperopic, and No Lens eyes, though there were differences in the intensity of labeling between groups. Early in the development of myopia (within the first 2 days of minus lens wear) and during the greatest increase in axial size and refractive error (see Figure 1), a significantly greater expression of AQP4 was seen in myopic eyes (as a ratio of experimental to fellow eyes) compared to hyperopic eyes in the NFL (t(21)=2.142, p<0.05; Figure 4B and Figure 5A). Positive immunoexpression in both hyperopic eyes and No Lens controls did not significantly differ in either the NFL or IPL (Figure 4B and Figure 5A). This difference in AQP4 expression in minus defocused eyes only existed early in development, and by day 4, no differences were seen in AQP4 expression. This lack of difference coincides with the general decrease in the rate of eye growth that begins after the compensatory myopic refractive error has been well established, as shown in Figure 1. No significant differences were seen in the level of AQP4 expression in the IPL, suggesting that AQP4 upregulation only occurs at the endfeet of Müller cells at the vitreal border in growing eyes.


Spatial and temporal dissociation of AQP4 and Kir4.1 expression during induction of refractive errors.

Goodyear MJ, Crewther SG, Murphy MJ, Giummarra L, Hazi A, Junghans BM, Crewther DP - Mol. Vis. (2010)

Comparison of the spatial and temporal distribution of AQP4 and Kir4.1 channel expression during the induction of refractive compensation to optical defocus (using pixel intensity analysis of stained sections). Blue stars indicate significant differences between the lens groups and/or control (No Lens) group (*p<0.05). Figures show the ratio mean luminance levels from the right eye (experimental eye) compared to the fellow left eye. A is the mean ratio luminance levels for AQP4 in the nerve fiber layer (NFL), B is the mean ratio luminance levels for Kir4.1 in the inner plexiform layer (IPL), C is the mean ratio luminance levels for Kir4.1 in sublamina A in the IPL, and D is the mean ratio luminance levels for Kir4.1 in sublamina B in the IPL.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2927440&req=5

f5: Comparison of the spatial and temporal distribution of AQP4 and Kir4.1 channel expression during the induction of refractive compensation to optical defocus (using pixel intensity analysis of stained sections). Blue stars indicate significant differences between the lens groups and/or control (No Lens) group (*p<0.05). Figures show the ratio mean luminance levels from the right eye (experimental eye) compared to the fellow left eye. A is the mean ratio luminance levels for AQP4 in the nerve fiber layer (NFL), B is the mean ratio luminance levels for Kir4.1 in the inner plexiform layer (IPL), C is the mean ratio luminance levels for Kir4.1 in sublamina A in the IPL, and D is the mean ratio luminance levels for Kir4.1 in sublamina B in the IPL.
Mentions: A similar regional distribution of AQP4 labeling was found between myopic, hyperopic, and No Lens eyes, though there were differences in the intensity of labeling between groups. Early in the development of myopia (within the first 2 days of minus lens wear) and during the greatest increase in axial size and refractive error (see Figure 1), a significantly greater expression of AQP4 was seen in myopic eyes (as a ratio of experimental to fellow eyes) compared to hyperopic eyes in the NFL (t(21)=2.142, p<0.05; Figure 4B and Figure 5A). Positive immunoexpression in both hyperopic eyes and No Lens controls did not significantly differ in either the NFL or IPL (Figure 4B and Figure 5A). This difference in AQP4 expression in minus defocused eyes only existed early in development, and by day 4, no differences were seen in AQP4 expression. This lack of difference coincides with the general decrease in the rate of eye growth that begins after the compensatory myopic refractive error has been well established, as shown in Figure 1. No significant differences were seen in the level of AQP4 expression in the IPL, suggesting that AQP4 upregulation only occurs at the endfeet of Müller cells at the vitreal border in growing eyes.

Bottom Line: Positive lens-wearing eyes showed reduced ocular growth compared to normal controls and developed a hyperopic refraction.Kir4.1 channel upregulation in the inner plexiform layer was only found on day 4 of positive lens wear during the development of refractive hyperopia.Increased AQP4 expression in the nerve fiber layer is suggested to contribute to the rapid axial elongation and movement of fluid into the vitreous cavity in the presence of minus lenses; whereas, upregulation of Kir4.1 channels appears to play a role in limiting axial elongation in the presence of plus lenses.

View Article: PubMed Central - PubMed

Affiliation: School of Psychological Sciences, La Trobe University, Melbourne, Victoria, Australia.

ABSTRACT

Purpose: Spatial co-localization of aquaporin water channels (AQP4) and inwardly rectifying potassium ion channels (Kir4.1) on the endfeet regions of glial cells has been suggested as the basis of functionally interrelated mechanisms of osmoregulation in brain edema. The aim of this study was to investigate the spatial and temporal changes in the expression of AQP4 and Kir4.1 channels in an avascular retina during the first week of the optical induction of refractive errors.

Methods: Three-day-old hatchling chicks were randomly assigned to three groups and either did not wear lenses or were monocularly goggled with +/-10D lenses for varying times up to 7 days before biometric assessment. Retinal tissue was prepared either for western blot analysis to show the presence of the AQP4 and Kir4.1 protein in the chick retina or for immunolocalization using AQP4 and Kir4.1 antibodies to determine the regional distribution and intensity of labeling during the induction of refractive errors.

Results: As expected, ultrasonography demonstrated that all eyes showed rapid elongation post hatching. Negative lens-wearing eyes elongated faster than fellow eyes or normal non goggled eyes and became progressively more myopic with time post lensing. Positive lens-wearing eyes showed reduced ocular growth compared to normal controls and developed a hyperopic refraction. Quantitative immunohistochemistry revealed the upregulation of AQP4 channel expression on Müller cells in the retinal nerve fiber layer during the first 2 days of negative lens wear. Kir4.1 channel upregulation in the inner plexiform layer was only found on day 4 of positive lens wear during the development of refractive hyperopia.

Conclusions: These results indicate that the expression of AQP4 and Kir4.1 channels on Müller cells is associated with the changes in ocular volume seen during the induction of refractive errors. However, the sites of greatest expression and the temporal pattern of the upregulation of AQP4 and Kir4.1 were dissimilar, indicating a dissociation of AQP4 and Kir4.1 function during refractive error development. Increased AQP4 expression in the nerve fiber layer is suggested to contribute to the rapid axial elongation and movement of fluid into the vitreous cavity in the presence of minus lenses; whereas, upregulation of Kir4.1 channels appears to play a role in limiting axial elongation in the presence of plus lenses.

Show MeSH
Related in: MedlinePlus