Format

Send to

Choose Destination
Exp Eye Res. 2018 Oct;175:32-41. doi: 10.1016/j.exer.2018.06.006. Epub 2018 Jun 5.

Expression of dopamine D2 and D3 receptors in the human retina revealed by positron emission tomography and targeted mass spectrometry.

Author information

1
Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8, Canada; Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8, Canada. Electronic address: fern.caravaggio@mail.utoronto.ca.
2
Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8, Canada; Molecular and Cellular Cognition Lab, German Center for Neurodegenerative Diseases(DZNE), Bonn, Germany.
3
Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8, Canada; Department of Pharmacology and Toxicology, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8, Canada.
4
Retina Department, Clínica David-Unidad Oftalmológica, Morelia, Mexico.
5
Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8, Canada; Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8, Canada.

Abstract

Dopamine D2 receptors (D2R) are expressed in the human retina and play an important role in the modulation of neural responses to light-adaptation. However, it is unknown whether dopamine D3 receptors (D3R) are expressed in the human retina. Using positron emission tomography (PET), we have observed significant uptake of the D3R-preferring agonist radiotracer [11C]-(+)-PHNO into the retina of humans in vivo. This led us to examine whether [11C]-(+)-PHNO binding in the retina was quantifiable using reference tissue methods and if D3R are expressed in human post-mortem retinal tissue. [11C]-(+)-PHNO data from 49 healthy controls (mean age: 39.96 ± 14.36; 16 female) and 12 antipsychotic-naïve patients with schizophrenia (mean age: 25.75 ± 6.25; 4 female) were analyzed. We observed no differences in [11C]-(+)-PHNO binding in the retina between first-episode, drug-naïve patients with schizophrenia and healthy controls. Post-mortem retinal tissues from four healthy persons (mean age: 59.75 ± 9.11; 2 female) and four patients with schizophrenia (mean age: 54 ± 17.11; 2 female) were analyzed using a targeted mass spectrometry technique: parallel reaction monitoring (PRM) analysis. Using targeted mass spectrometry, we confirmed that D3R are expressed in human retinal tissue ex vivo. Notably, there was far greater expression of D2R relative to D3R in the healthy human retina (∼12:1). Moreover, PRM analysis revealed reduced D2R, but not D3R, expression in the retinas of non-first episode patients with schizophrenia compared to healthy controls. We confirm that D3R are expressed in the human retina. Future studies are needed to determine what proportion of the [11C]-(+)-PHNO signal in the human retina in vivo is due to binding to D3R versus D2R. Knowledge that both D2R and D3R are expressed in the human retina, and potentially quantifiable in vivo using [11C]-(+)-PHNO, poses new research avenues for better understanding the role of retinal dopamine in human vision. This work may have important implications for elucidating pathophysiological and antipsychotic induced visual deficits in schizophrenia.

PMID:
29883636
PMCID:
PMC6167174
[Available on 2019-10-01]
DOI:
10.1016/j.exer.2018.06.006
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center