TY - JOUR
T1 - Form-Deprivation and Lens-Induced Myopia Are Similarly Affected by Pharmacological Manipulation of the Dopaminergic System in Chicks
AU - Thomson, Kate
AU - Karouta, Cindy
AU - Ashby, Regan
N1 - Funding Information:
Partially funded by ANU Connect Ventures through a Discovery Translation Fund grant (Project ID: DTF311).
Publisher Copyright:
Copyright 2020 The Authors.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/10
Y1 - 2020/10
N2 - Purpose: Animal models have demonstrated a link between decreases in retinal dopamine levels and the development of form-deprivation myopia (FDM). However, the consistency of dopamine's role in the other major form of experimental myopia, that of lens-induced myopia (LIM), is less clear, raising the question as to what extent dopamine plays a role in human myopia. Therefore, to better define the role of dopamine in both forms of experimental myopia, we examined how consistent the protection afforded by dopamine and the dopamine agonist 6-amino-5,6,7,8-tetrahydronaphthalene-2,3-diol hydrobromide (ADTN) is between FDM and LIM. Methods: Intravitreal injections of dopamine (0.002, 0.015, 0.150, 1.500 µmol) or ADTN (0.001, 0.010, 0.100, 1.000 µmol) were administered daily to chicks developing FDM or LIM. Axial length and refraction were measured following 4 days of treatment. To determine the receptor subtype by which dopamine and ADTN inhibit FDM and LIM, both compounds were coadministered with either the dopamine D2-like antagonist spiperone (0.005 µmol) or the D1-like antagonist SCH-23390 (0.005 µmol). Results: Intravitreal administration of dopamine or ADTN inhibited the development of FDM (ED50 = 0.003 µmol and ED50 = 0.011 µmol, respectively) and LIM (ED50 = 0.002 µmol and ED50 = 0.010 µmol, respectively) in a dose-dependent manner, with a similar degree of protection observed in both paradigms (P = 0.471 and P = 0.969, respectively). Coadministration with spiperone, but not SCH-23390, inhibited the protective effects of dopamine and ADTN against the development of both FDM (P = 0.214 and P = 0.138, respectively) and LIM (P = 0.116 and P = 0.100, respectively). Conclusions: pharmacological targeting of the retinal dopamine system inhibits FDM and LIM in a similar dose-dependent manner through a D2-like mechanism.
AB - Purpose: Animal models have demonstrated a link between decreases in retinal dopamine levels and the development of form-deprivation myopia (FDM). However, the consistency of dopamine's role in the other major form of experimental myopia, that of lens-induced myopia (LIM), is less clear, raising the question as to what extent dopamine plays a role in human myopia. Therefore, to better define the role of dopamine in both forms of experimental myopia, we examined how consistent the protection afforded by dopamine and the dopamine agonist 6-amino-5,6,7,8-tetrahydronaphthalene-2,3-diol hydrobromide (ADTN) is between FDM and LIM. Methods: Intravitreal injections of dopamine (0.002, 0.015, 0.150, 1.500 µmol) or ADTN (0.001, 0.010, 0.100, 1.000 µmol) were administered daily to chicks developing FDM or LIM. Axial length and refraction were measured following 4 days of treatment. To determine the receptor subtype by which dopamine and ADTN inhibit FDM and LIM, both compounds were coadministered with either the dopamine D2-like antagonist spiperone (0.005 µmol) or the D1-like antagonist SCH-23390 (0.005 µmol). Results: Intravitreal administration of dopamine or ADTN inhibited the development of FDM (ED50 = 0.003 µmol and ED50 = 0.011 µmol, respectively) and LIM (ED50 = 0.002 µmol and ED50 = 0.010 µmol, respectively) in a dose-dependent manner, with a similar degree of protection observed in both paradigms (P = 0.471 and P = 0.969, respectively). Coadministration with spiperone, but not SCH-23390, inhibited the protective effects of dopamine and ADTN against the development of both FDM (P = 0.214 and P = 0.138, respectively) and LIM (P = 0.116 and P = 0.100, respectively). Conclusions: pharmacological targeting of the retinal dopamine system inhibits FDM and LIM in a similar dose-dependent manner through a D2-like mechanism.
KW - ADTN
KW - Animal models
KW - Dopamine
KW - Myopia
KW - Ocular growth
KW - Refractive error
UR - http://www.scopus.com/inward/record.url?scp=85092679097&partnerID=8YFLogxK
U2 - 10.1167/iovs.61.12.4
DO - 10.1167/iovs.61.12.4
M3 - Article
C2 - 33016984
AN - SCOPUS:85092679097
SN - 1552-5783
VL - 61
SP - 1
EP - 13
JO - Investigative ophthalmology & visual science
JF - Investigative ophthalmology & visual science
IS - 12
M1 - 2770875
ER -