Targeting ASICs in Optic Neurodegenerative Diseases is Neuroprotective

Glaucoma is the second leading cause of blindness in the US. Currently, glaucoma drugs can lower pressure in the eye; however, vision loss continues. There is an urgent need for newer drugs that can save the neurons in the eye following any eye injury. The current project will attempt developing such novel drugs.

The goal of the current study is to test whether the acid-sensing ion channel (ASIC), inhibitors may exert protective effects in the retina.

Under Aim 1, we will determine the neuroprotective effects of an ASIC1 inhibitor (eg, psalmotoxin) following injury. Retinal ganglion function will be measured by pattern ERG and optic nerve damage will be assessed using benzene P –Phenylenediamine (PPD) staining. Retinal layer thickness will be monitored by hematoxylin and eosin (H&E) staining.

For Aim 2, we will determine the neuroprotective effects of ASIC1/2 knockdown using shRNA lentiviral particles following retinal injuries. Retinal ganglion function will be measured by pattern ERG. Also, axonal integrity will be analyzed using PPD staining.

If successful, ASIC inhibitors may represent a new class of neuroprotective drugs in the fight against glaucoma. In addition, the use of lentiviral particles may act as an alternate therapy when selectively targeting the retinal ganglion cells. Such therapy may also be tested in other retinal neurodegenerative diseases.

Once this study is completed, there will be hope for a new class of glaucoma drugs that can be used alone or in combination with the current ones. However, current drugs only act by lowering intraocular pressure. Therefore, there is an urgent need for neuroprotective drugs and AISC inhibitors may serve that need.