Impact of ADP-ribose analog INV-102 on Retinal Ganglion Cell Transport Function in Glaucoma
04/09/2019Glaucoma, a pathologic condition associated with increased intraocular pressure (IOP), affects more than 2.5 million Americans. The increased IOP results from accumulation of aqueous humor in the region between the iris and the cornea. Due to its prevalence and lack of a cure, alternative preventative treatments are necessary in clinical practice. Our lab group aimed to study the potential efficacy of the Invirsa compound INV-102 to preserve the cells impacted by increased IOP, the retinal ganglion cells. An experimental trial was done in a rat glaucoma model consisting of four treatment groups: negative control, treated with PBS qd; positive control, treated with Bimatoprost ophthalmic solution qd; INV-102, 1%, qd; and INV-102, 1%, bid. Measure of therapeutic effect was done by quantifying RGC and axon number, and RGC transport function in retinal tissue, optic nerve, and the superior colliculi (SC) in the brain. Further, mRNA and protein expression of markers of inflammation, oxidative stress, and energy-associated genes and proteins [AMPK, PGC-1α, NAD+] were also measured. RGC functional evaluation was done using afluorescent dye known as Cholera Toxin B, or CTB, that was intraocularly injected into each rat, picked up by the RGCs, and then transported anterogradely to the SC. Analyzing sectioned SC allowed for CTB intensity to be calculated, reflecting the transport function of RGCs. Our lab group predicted that rats treated with INV-102 will have less RGC degeneration and improved CTB transport over controls.