Revisiting cannabinoid receptor 2 expression and function in murine retina

NEUROPHARMACOLOGY

卷:141

Article

Borowska-Fielding, Joanna²  Murataeva, Natalia¹  Smith, Ben³  Szczesniak, Anna-Maria²  Leishman, Emma¹  Daily, Laura¹  Toguri, J. Thomas²  Hillard, Cecelia J.⁴  Romero, Julian⁵  Bradshaw, Heather¹  Kelly, Melanie E. M.^2,3,6  Straiker, Alex¹ 

[1] Indiana Univ, Gill Ctr Biomol Sci, Dept Psychol & Brain Sci, Bloomington, IN USA

[2] Dalhousie Univ, Dept Pharmacol, Halifax, NS, Canada

[3] Dalhousie Univ, Physiol & Biophys, Halifax, NS, Canada

[4] Med Coll Wisconsin, Dept Pharmacol & Toxicol, Milwaukee, WI 53226 USA

[5] Univ Francisco de Vitoria, Fac Expt Sci, Madrid 28223, Spain

[6] Dalhousie Univ, Anesthesia, Halifax, NS, Canada

关键词: Cannabinoid;    CB2;    Retina;    Electroretinogram;    ERG;   

DOI  :  10.1016/j.neuropharm.2018.08.007

来源: Elsevier

【 摘 要 】

The cannabinoid receptor CB2 plays a significant role in the regulation of immune function whereas neuronal expression remains a subject of contention. Multiple studies have described CB2 in retina and a recent study showed that CB2 deletion altered retinal visual processing. We revisited CB2 expression using immunohistochemistry and a recently developed CB2-eGFP reporter mouse. We examined the consequence of acute vs. prolonged CB2 deactivation on the electroretinogram (ERG) responses. We also examined lipidomics in CB2 knockout mice and potential changes in microglia using Scholl analysis. Consistent with a published report, in CB2 receptor knockout mice see an increased ERG scotopic a-wave, as well as stronger responses in dark adapted cone-driven ON bipolar cells and, to a lesser extent cone-driven ON bipolar cells early in light adaptation. Significantly, however, acute block with CB2 antagonist, AM630, did not mimic the results observed in the CB2 knockout mice whereas chronic (7 days) block did. Immunohistochemical studies show no CB2 in retina under non-pathological conditions, even with published antibodies. Retinal CB2 eGFP reporter signal is minimal under baseline conditionsbut upregulated by intraocular injection of either LPS or carrageenan. CB2 knockout mice see modest declines in a broad spectrum of cannabinoid-related lipids. The numbers and morphology of microglia were unaltered. In summary minimal CB2 expression is seen in healthy retina. CB2 appears to be upregulated under pathological conditions. Previously reported functional consequences of CB2 deletion are an adaptive response to prolonged blockade of these receptors. CB2 therefore impacts retinal signaling but perhaps in an indirect, potentially extra-ocular fashion.

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