During development, the eye grows until incoming light is focused on the retina, a process called emmetropization. Dopamine (DA) has been heavily implicated as a modulator of this process. While many studies have utilized pharmacological agents and neurotoxins to elucidate the exact role of dopamine on eye growth, much remains to be known about this process. In this study, a retina-specific dopamine knockout is utilized to characterize the role of dopamine in refractive development, ocular growth, and susceptibility to experimental myopia. Dopamine knockout (rTHKO) mice were on a C57BL/6J background and were homozygous for both the Chx10 Cre-recombinase and floxed tyrosine hydroxylase alleles. In the untreated refractive development (RD) paradigm, rTHKO mice and age-matched control (Ctrl) mice were measured every 2 weeks from post-natal day 28 (P28) to P112. Under the FD paradigm, mice received a head-mounted diffuser goggle at P28 over their right eye (OD) and were measured weekly until P77. Measurements of refractive error, corneal curvature, and ocular biometrics were obtained at each measurement session. Retinas from each group were analyzed by HPLC for dopamine and DOPAC concentrations. rTHKO mice exhibited an 85.3% loss in retinal DOPAC and an 89.5% loss in retinal DA compared to Ctrl mice. Untreated rTHKO mice became spontaneously myopic (F(1,188) = 7.602, p<0.001) and had significantly steeper corneas (Main effect of genotype F(1,209) = 14.1, p<0.001) compared to Ctrl mice. rTHKO 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). Form deprived rTHKO and Ctrl mice showed statistically similar myopic shifts (difference of right and left eyes). Our results support the hypothesis that dopamine is a stop signal for refractive development. Loss of dopamine may affect the growth of the cornea, which would heavily impact refractive state. It is possible that the rTHKO mice show slowed axial growth due to myopic defocus imposed by the corneal steepening but were unable to fully compensate for the myopic defocus. Interestingly, the reduction in DA did not influence the response to FD.
Table of Contents
Introduction: 1 Materials and Methods: 4 Retinal Dopamine Knockout Model: 4 Experimental Overview: 5 Ocular Measurement: 5 Dopamine Analysis: 7 Head Pedestal Surgery: 8 Statistics: 9 Results: 10 Refractive Development: 10 Dopamine Analysis: 10 Form Deprivation: 11 Discussion: 11 Retinal Dopamine Knockout Effectiveness: 11 Corneal Steepening Underlies Myopic Refraction in rTHKO: 12 Dopamine's Effect on Myopia and Form Deprivation: 14 Future Directions: 16 Figures: 17 Figure 1: 17 Figure 2: 17 Figure 3: 18 Figure 4: 18 Figure 5: 19 Figure 6: 19 Appendix: 20 Abbreviations: 20 References: 21
About this Honors Thesis
|Committee Chair / Thesis Advisor|
|The Role of Dopamine in the Development of Myopia ()||2018-08-28||