Retinal Toxicity Induced by a Novel β-secretase Inhibitor in the Sprague-Dawley Rat.

β-Secretase 1 (BACE1) represents an attractive target for the treatment of Alzheimer's disease. In the course of development of a novel small molecule BACE1 inhibitor (AMG-8718), retinal thinning was observed in a 1-month toxicity study in the rat. To further understand the lesion, an investigational study was conducted whereby rats were treated daily with AMG-8718 for 1 month followed by a 2-month treatment-free phase.

Primate Retinal Signaling Pathways: Suppressing ON-Pathway Activity in Monkey With Glutamate Analogues Mimics Human CSNB1-NYX Genetic Night Blindness.

Retinal on-pathway dysfunction is implicated in human complete-type congenital stationary night blindness (CSNB1), a Mendelian genetic condition that results from mutations in the NYX gene encoding the protein nyctalopin. We probed cone pathway dysfunction in four human genotyped CSNB1 affected males by electroretinogram (ERG) recordings elicited with photopic sinusoidal and rapid-on/off-ramp flicker stimuli that are reputed to elicit on/off-pathway activity selectively. Results were analyzed in relation to ERG abnormalities created in anesthetized non-human primates by intravitreal application of glutamate analogues that selectively suppress retinal on- or off-pathway bipolar cell activity.