Category
Poster - Basic
Description
Glaucoma – an eye disease characterized by increased intraocular pressure (IOP) – is the second leading cause of blindness internationally. Patients experience acute damage to the optic nerve causing blindness, however, lowering the intraocular pressure of the eye can allow for less progressive retinal ganglion loss. Cannabinoid receptors 1 and 2 (CB1 and CB2) are G protein coupled receptors that are found in the glaucoma affected areas in the eye. These endocannabinoid receptors are activated by agonists anandamide (AEA) and 2-arachyidonoylglycerol (2-AG), which according to literature contain promising retinal ganglion cell protective properties. Endocannabinoids have been observed to increase blood flow to the optic nerve head which could potentially be vasoprotective and benefit the altered hemodynamics seen in glaucoma. AEA and 2-AG are broken down by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), which leads to increased IOP, therefore, the primary goal of this project is to design and synthesize peripherally selective (unable to cross the blood brain barrier) FAAH and MAGL inhibitors. Our research involves novel synthetic methods to synthesize sulfonamide compounds to inhibit the breakdown of the agonists. The compounds made were tested for confirmation of inhibitive properties via a FAAH kit, which utilized a known inhibitor to compare efficacy. Increasing the number of cannabinoids by way of enzyme inhibition would be expected to lower intraocular pressure in glaucoma patients, which is the preferred outcome. Future plans include evaluating the efficacy of the synthesized compounds to inhibit MAGL via a kit of similar nature. Our ongoing research is focused on modifying the southern region of previously identified sulfonamides.
Design and Synthesis of Endocannabinoid Enzyme Inhibitors for Potential Peripherally Selective Glaucoma Treatments
Poster - Basic
Glaucoma – an eye disease characterized by increased intraocular pressure (IOP) – is the second leading cause of blindness internationally. Patients experience acute damage to the optic nerve causing blindness, however, lowering the intraocular pressure of the eye can allow for less progressive retinal ganglion loss. Cannabinoid receptors 1 and 2 (CB1 and CB2) are G protein coupled receptors that are found in the glaucoma affected areas in the eye. These endocannabinoid receptors are activated by agonists anandamide (AEA) and 2-arachyidonoylglycerol (2-AG), which according to literature contain promising retinal ganglion cell protective properties. Endocannabinoids have been observed to increase blood flow to the optic nerve head which could potentially be vasoprotective and benefit the altered hemodynamics seen in glaucoma. AEA and 2-AG are broken down by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), which leads to increased IOP, therefore, the primary goal of this project is to design and synthesize peripherally selective (unable to cross the blood brain barrier) FAAH and MAGL inhibitors. Our research involves novel synthetic methods to synthesize sulfonamide compounds to inhibit the breakdown of the agonists. The compounds made were tested for confirmation of inhibitive properties via a FAAH kit, which utilized a known inhibitor to compare efficacy. Increasing the number of cannabinoids by way of enzyme inhibition would be expected to lower intraocular pressure in glaucoma patients, which is the preferred outcome. Future plans include evaluating the efficacy of the synthesized compounds to inhibit MAGL via a kit of similar nature. Our ongoing research is focused on modifying the southern region of previously identified sulfonamides.
Comments
Undergraduate