Abstract
Purpose :
Diabetic Macular Edema (DME) is a common cause of vision loss. Hyperglycemia leads to carbonyl stress in the retina, resulting in accumulation of toxic aldehydes such as methylglyoxal, 4-hydroxy-trans-2-nonenal, and malondialdehyde, which induce inflammatory changes in the eye, including the development of DME. The ability of the novel aldehyde trap, ADX-103, to treat diabetic ocular inflammation was tested in a rat streptozotocin (STZ)-induced model of DME.
Methods :
Brown Norway rats were administered STZ for six weeks to induce diabetes. ADX-103 or vehicle was administered by intravitreal (IVT) injection at Weeks 6 and 8. Non-diabetic rats did not receive any treatment and served as a negative control. Retinal thickness, vascularity, and function were monitored weekly by optical coherence tomography (OCT) and fundus angiography (FA), from Weeks 6 through 10; electroretinograms (ERG) were generated at Week 6, 8 and 10. Rats were sacrificed at Week 10, and retinas were processed for histopathology.
Results :
At Week 8, retinal thickness and vascular leakage assessed by OCT and FA slightly increased in the STZ-induced rat model, and mean vascular scores were 3.00 for the control group and 2.47 (p<0.05) in the ADX-103-treated group. At Week 8 and 9, retinal thickness and vascular leakage scores were decreased in the ADX-103-treated group although not statistically significant from control. At Week 10, histopathological assessment indicated significantly reduced retinal thickness (p<0.0001) in the ADX-103-treated group. The decrease in retinal inflammation was accompanied by a significant reduction in neutrophil infiltration compared to vehicle (p<0.0001). In addition, retinal vascularity score decreased by 36% (p<0.05) in the ADX-103-treated group compared to vehicle. STZ did not induce ERG changes, nor were there any ERG changes in the ADX-103- or vehicle-treated groups relative to the non-diabetic control group. ADX-103 appeared to be well tolerated in the retina.
Conclusions :
ADX-103 decreased retinal inflammation, blocked neutrophil infiltration, and blocked retinal vascular changes in this model of DME. The data suggest that aldehyde sequestration represents a novel therapeutic approach for the treatment of the ophthalmic inflammatory sequelae of diabetes.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.