Retina and Optic Nerve Research Laboratory

Research at Dalhousie Medical School

Kelly Lab

The role of cannabinoids in ocular inflammation


Dr. Melanie Kelly is a professor in the Departments of Pharmacology, Ophthalmology and Visual Sciences, and Anesthesia, Perioperative Medicine & Pain Management at Dalhousie University.The Kelly Lab is investigating ocular inflammation and the anti-inflammatory role of cannabinoid receptor by using selective cannabinoid 2 receptor (CB2R) agonists.

Professor Kelly’s laboratory is located in a collaborative, multidisciplinary vision laboratory called the Retina and Optic Nerve Research Laboratory within the Faculty of Medicine at Dalhousie University.




Research expertise

Dr. Kelly’s primary research expertise is molecular and functional pharmacology, specifically receptors and cell signaling pathways with a special interest in translational pharmacology.

Dr. Kelly’s work has examined pathways important in survival of retinal ganglion cells in experimental models of glaucoma and has made use of gene mutations to explore signaling pathways involved in retinal progenitor cell growth and development.

She has contributed to knowledge on G protein coupled signaling pathways, important in the regulation of various ocular functions including aqueous humor secretion, and outflow and retinal vascular function.

Current research

Current research addresses the pharmacology of the endocannabinoids and lipid signaling in the mammalian eye with a specific focus on:

  • regulation of intraocular pressure
  • retinal neurovascular signaling
  • ocular microcirculation
  • ocular inflammatory diseases (uveitis, uveoretinitis, proliferative vitreoretinopathy)
  • vasculopathies

Professor Kelly’s laboratory has experience working with both in vitro and in vivo models of retinal and anterior segment disease. Research methodologies used in the laboratory include:

  • immunohistochemistry
  • bioluminescence resonance energy transfer (BRET)
  • fluorescence resonance energy transfer (FRET)
  • fluorescence ion imaging
  • patch-clamp electrophysiology
  • In-cell and On-cell Western
  • PCR
  • biochemical assays of cell signaling proteins and enzyme activity
  • cell culture
  • isolated microvasculature preparations
  • intraocular pressure measurement
  • intravital in vivo imaging

Learn more

Publications

  • Hudson, B., Hébert, T., Kelly, M.E.M. (2010). Physical and Functional Interaction between the CB1 cannabinoid receptor and the β2 adrenergic receptor. Brit. J. Pharmacol. 160: 627-642. Hudson, B. and Kelly, M.E.M. (2010). Ligand and heterodimer directed functional selectivity of the CB1 Cannabinoid receptor. Mol. Pharmacol. 77: 1-9.
  • Almasieh, M., Zhou, Y., Kelly, M.E.M., Casanova, C., Di Polo, A. (2010). Galantamine promotes structural and functional neuroprotection in glaucoma via activation of muscarinic, but not nicotinic, acetylcholine receptors. Cell Death & Disease 1 (e27): 1-11.
  • Hudson, B., Beazley, M., Szezcesnaick, A., Straiker, A., Kelly, M.E.M. (2011). Indirect sympatholytic actions at β-adrenoceptors account for the ocular hypotensive actions of cannabinoid receptor agonists. J. Pharmacol. Exp. Therap. 339: 757-767.
  • Lehmann, C., Kianian, M., Cerny, V., Zhuo, J., Kelly, M.E.M. (2011). The endocannabinoid system in sepsis: a potential target to improve microcirculation SIGNA VITAE 6 (1): 7-13. 16.
  • Szezesniack, A., Maor, Y., Robertson, H.A., Kelly, M.E.M. (2011). The non-pyschotropic cannabinoids, abnormal cannabidiol and canabigerol-DMH lower intraocular pressure independent of cannabinoid receptor 1 and 2 activation. J. Ocular Pharmacol. Therapeutics 27:427-435.
  • MacIntyre, J.N., Slusar, J.E., Dong, A.X., Zhu, J-Q., Howlett, S.E., Kelly, M.E.M. (2012). Age-associated remodeling of retinal arterioles differs between the sexes. Mechanisms of Aging and Develop. 133(9-10): 611-619.
  • LaPrairie, R., Kelly, M.E.M, Denovan-Wright, E. (2012). Differential regulation of type 1 cannabinoid receptor transcription during development, pathogenesis, and pharmacological manipulation. Brit. J. Pharmacol. 167(8): 1583-1595.
  • Küster, I., Kuschnereit, R., Kelly, MEM., Zhou, J. Whynot, S., Kianian, M., Hung, O., Shukla, R., Cerny, V., Pavlovic, D., Lehmann, C. (2012). Cannabinoid 1 receptor causes seizures during anesthesia in experimental sepsis. Anesth. Analg. 114: 1217-1219.
  • Lehmann, C., Kianian, M., Zhou, J., Küster, I., Kuschnereit, R., Whynot, S., Hung, O., Shukla, R., Johnston, B., Cerny, V., Pavlovic, D., Spassov, A. Kelly, M.E.M. (2012). Cannabinoid receptor 2 activation reduces intestinal leukocyte recruitment and systemic inflammatory mediator release in acute experimental sepsis. Crit. Care 15: 16(2): R47 doi: 10.1186/cc11248.
  • Hudson, B., Kelly, M.E.M. (2012). Identification of Novel Competing β2AR pERK Signalling Pathways in Human Trabecular Meshwork Cells. J. Ocular Pharmacol. 28(1): 17-25.
  • Al-Banna, N.A., Pavlovic, D., Gründling, M., Zhou, J., Kelly, M., Whynot, S., Hung, O., Johnston, B., Issekutz, T.B., Kern, H., Cerny, V., Lehmann, C.H. (2013). Impact of antibiotics on the microcirculation in local and systemic inflammation. Clin Hemorheol Microcirc. 53(1-2):155-169.
  • Dranse, H., Kelly, M.E.M., Hudson, B. (2013). Drugs or Diet?- Developing Novel Therapeutic Strategies Targeting the Free Fatty Acid Family of GPCRs. Brit. J. Pharmacol. 170(4):696-711. Slusar, J.E., Szczesniack, A., Cairns, E., Bradshaw, H., Di Polo, A., Kelly, M.E.M. (2013). The fatty acid amide hydrolase inhibitor, URB597, promotes retinal ganglion cell neuroprotection in a rat model of optic nerve axotomy. Neuropharmacol. 72: 116-125.
  • Kianian, M., Al-Bana, N.A., Kelly, M.E.M., Lehmann, C. (2013). Inhibition of endocannabinoid degradation in experimental endotoxemia reduces leucocyte adhesion and improves capillary perfusion in the gut. J. Basic Clin. Physiol. Pharmacol. 24(1): 27-33.
  • Kelly, M.E.M., McIntosh, B. Straiker, A. (2013). Ocular actions of Cannabis sativa and constituent phytocannabinoids. In: AHP Monograph and Therapeutic Compendium on Cannabis sativa-C indica. Eds: Upton, Romm, Russo and Craker. AHP, Scotts Valley, CA. Website: www.herbal-ahp.org (in press)
  • Cerny, V., Zhou, J., Kelly, M.E.M., Alotibi, I., Zdenek Turek, Z., Whynot, S., Saleh, I.A., Lehmann, C.H. (2013). Noninvasive assessment of the iridial vessels in rats using sidestream dark-field imaging. J. Microscopy 249(2): 119-123.
  • Al-Banna, N.A., Toguri, J.T., Kelly, M.E., Lehmann, C. (2013). Leukocyte-endothelial interactions within the ocular microcirculation in inflammation and infection. Clin Hemorheol Microcirc. [Epub ahead of print] PubMed PMID: 24113507.
  • Bagher, A.M., Laprairie, R.B., Kelly, M.E., Denovan-Wright, E.M. (2013). Co-expression of the human cannabinoid receptor coding region splice variants (hCB(1)) affects the function of hCB(1) receptor complexes. Eur J Pharmacol. 721:341-354.
  • Caldwell, M.D., Hu, S.S., Viswanathan, S., Bradshaw, H, Kelly, M.E.M., Straiker, A. (2013). A GPR18-based signaling system regulates IOP in murine eye. Brit. J. Pharmacol. 169: 834-843.
  • Kianian, M., Al-Banna, N.A., Kelly, M.E., Lehmann, C. (2013). Inhibition of endocannabinoid degradation in experimental endotoxemia reduces leukocyte adhesion and improves capillary perfusion in the gut. J Basic Clin Physiol Pharmacol. 24:27-33.
  • Laprairie, R.B., Kelly, M.E.M., Denovan-Wright, E.M. (2013). Cannabinoids induce type 1 cannabinoid receptor expression in cell culture models of Huntington’s disease. Mol. Pharmacol. 72: 47-57.
  • Almasieh, M., McIntyre, J.N., Pouliot, M., Casanova, C., Vaucher, E., Kelly, M.E.M., Di Polo, A. (2013). Acetylcholinesterase inhibition promotes retinal vasoprotection and increases in ocular blood flow in experimental glaucoma. Invest. Ophthalmol. Vis. Sci. 54.5: 3171-3183.
  • Sardinha, J., Lehmann, C., Kelly, M.E. (2013). "Targeting the Endocannabinoid System to Treat Sepsis." SIGNA VITAE 8.1: 9-14.
  • Laprairie RB, Bagher AM, Kelly ME, Dupré DJ, Denovan-Wright EM (2014). Type 1 Cannabinoid Receptor Ligands Display Functional Selectivity in a Cell Culture Model of Striatal Medium Spiny Projection Neurons. J Biol Chem. Jul 18. pii:jbc.M114.557025. [Epub ahead of print] PubMed PMID: 25037227.
  • Laprairie RB, Warford JR, Hutchings S, Robertson GS, Kelly ME, Denovan-Wright EM (2014). The cytokine and endocannabinoid systems are co-regulated by NF-κB p65/RelA in cell culture and transgenic mouse models of Huntington's disease and in striatal tissue from Huntington's disease patients. J Neuroimmunol. 267(1-2):61-72.
  • Toguri J T, Lehmann C, Laprairie R B, Szczesniak A M, Zhou J, Denovan-Wright E M, Kelly M E M (2014) Anti-inflammatory effects of Cannabinoid 2 Receptor activation in endotoxin-induced uveitis. British Journal of Pharmacology. 171(6):1448-61.

See the full publication list in PubMed

Collaborations

  • Dr. Christian Lehman, Dept. Anesthesia and Pharmacology, Dalhousie University
  • Dr. Mary Lynch, Dept. Anesthesia and Pharmacology, Dalhousie University
  • Dr. Orlando Hung, Dept. Anesthesia and Pharmacology, Dalhousie University
  • Dr. Vladimir Cerny, Dept. Anesthesia and Critical Care, Charles University, Prague, CzR
  • Dr. Dao-Yi Yu, Dept. Ophthalmology, University Western Australia
  • Dr. Eileen Denovan-Wright, Dept Pharmacology, Dalhousie University
  • Dr. Susan Howlett, Dept. Pharmacology, Dalhousie University
  • Dr. Jana Sawynok, Dept. Pharmacology, Dalhousie University
  • Dr. Jason McDougall, Dept. Anesthesia and Pharmacology, Dalhousie University
  • Dr. William Baldridge, Depts. Anatomy & Neurobiology & Ophthalmology, Dalhousie
  • University.
  • Dr. Heather Bradshaw, Indiana University, Bloomington
  • Dr. Alex Straiker, Indiana University, Bloomington
  • Dr. Raphael Mechoulam, Hebrew University, Jerusalem, Israel
  • Dr. Ganesh Thakur, Northeastern University, Boston, USA
  • Dr. Adriana Dipolo, Dept Pathology & Cell Biology, Université de Montréal
  • Dr. Lesya Shuba, Dept. Ophthalmology, Dalhousie University
  • Dr. Francois Tremblay, Dept. Ophthalmology, Dalhousie University
  • Dr. Steven Barnes, Dept. Physiology and Ophthalmology, Dalhousie University
  • Dr. Balwantray Chauhan, Dept. Ophthalmology, Dalhousie University
  • Dr. Terence Hébert, Dept. Pharmacology, McGill University