rTHKO mice exhibited significantly myopic refractions and steeper corneas compared to Ctrl mice.
Retina-specific knockout (rTHKO) mice showed myopic refractions at 4 and 6 weeks of age.
rTHKO mice had thinner corneas and retinas, and shorter axial lengths than control mice.
Dopamine levels in rTHKO retinas were less than 15% of those in control retinas, with a higher turnover rate.
Responses to form deprivation were similar for rTHKO and control mice, but more variable in rTHKO mice.
Simplified
PURPOSE: The neuromodulator (DA) has been implicated in the prevention of excessive ocular elongation and in various animal models. This study used retina-specific DA knockout mice to investigate the role of retinal DA in refractive development and susceptibility to experimental myopia.
METHODS: Measurements of refractive error, corneal curvature, and ocular biometrics were obtained as a function of age for both untreated and form-deprived (FD) groups of retina-specific tyrosine hydroxylase knockout (rTHKO) and control (Ctrl) mice. Retinas from each group were analyzed by HPLC for levels of DA and its primary metabolite (DOPAC).
RESULTS: Under normal visual conditions, rTHKO mice showed significantly myopic refractions (F(1,188) = 7.602, P < 0.001) and steeper corneas (main effect of genotype F(1,180) = 5.1, P < 0.01) at 4 and 6 weeks of age compared with Ctrl mice. Retina-specific THKO mice also had thinner corneas (main effect of genotype F(1,181) = 37.17, P < 0.001), thinner retinas (F(6,181) = 6.07, P < 0.001), and shorter axial lengths (F(6,181) = 3.78, P < 0.01) than Ctrl mice. Retina-specific THKO retinas contained less than 15% of DA and DOPAC compared with Ctrl retinas, and the remaining DA had a significantly higher turnover, as indicated by DOPAC/DA ratios (Student's t-test, P < 0.05). Retina-specific THKO mice showed similar, yet more variable, responses to 6 weeks of FD compared with Ctrl mice.
CONCLUSIONS: Diminished retinal DA induced spontaneous myopia in mice raised under laboratory conditions without form deprivation. The relative myopic shift in rTHKO mice may be explained by steeper corneas, an unexpected finding. The chronic loss of DA did not significantly alter the FD myopia response in rTHKO mice.
Key numbers
3.28 ± 0.27 D
Average Refractive Error Difference
Difference in refractive error between rTHKO and Ctrl mice under normal conditions
0.023 ± 0.003 mm
Corneal Radius of Curvature Difference
Comparison of corneal curvature between rTHKO and Ctrl mice
4.07 ± 1.5 D
Myopic Shift After Form Deprivation
Myopic shift in rTHKO mice after 6 weeks of form deprivation treatment
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