Search

Abstract Nonfibrillar amyloid-β oligomers (AβOs) are a major component of drusen, the sub-retinal pigmented epithelium (RPE) extracellular deposits characteristic of age-related macular degeneration (AMD), a common cause of global blindness. We report that AβOs induce RPE degeneration, a clinical hallmark of geographic atrophy (GA), a vision-threatening late stage of AMD that is currently untreatable. We demonstrate that AβOs induce activation of the NLRP3 inflammasome in the mouse RPE in vivo and that RPE expression of the purinergic ATP receptor P2RX7, an upstream mediator of NLRP3 inflammasome activation, is required for AβO-induced RPE degeneration. Two classes of small molecule inflammasome inhibitors—nucleoside reverse transcriptase inhibitors (NRTIs) and their antiretrovirally inert modified analog Kamuvudines—both inhibit AβOs-induced RPE degeneration. These findings crystallize the importance of P2RX7 and NLRP3 in a disease-relevant model of AMD and identify inflammasome inhibitors as potential treatments for GA.

Fluorescence lifetime imaging ophthalmoscopy (FLIO) is a novel technique that measures in vivo autofluorescence intensity decay over time of endogenous fluorophores in the retina. The Heidelberg Engineering FLIO system was used to obtain two 30 degree scans centered on the fovea of both eyes. The FLIO system uses a 473nm blue scanning laser light source and the emitted fluorescence is detected in two wavelengths channels, short and long spectral channels (SSC, LSC). Since the mydriatic status influence the FLIO result, the impact of mydriasis on FLIO need to be clarified. In this prospective, observational study, the impact of mydriasis on measurements from fluorescence lifetime imaging ophthalmoscope (FLIO) images in normal subjects were evaluated. 12 healthy participants (24 eyes) were volunteered and all subjects were scanned twice and the mean fluorescence lifetime (τm) values were computed with dilation and without dilation on different days. Intraclass correlation coefficients (ICC) and coefficients of variation (CV) were calculated from the measured τm in dilated, nondilated and between the dilated and non-dilated setting. Test duration was also compared and correlated with lifetimes in both settings. Repeatability was excellent for both the dilation and non-dilation settings (ICC; 0.967-0.996; 0.926-0.986, respectively). The agreement between the dilation and non-dilation settings, however, were lower (ICC; 0.688-0.970). The τm in the non-dilation setting was significantly longer than in the dilation setting for the SSC (P

Purpose. To compare the effects of physiologic versus pharmacologic pupil dilation on anterior chamber angle (ACA) measurements obtained with spectral domain optical coherence tomography (SD-OCT). Methods. Forty eyes from 20 healthy, phakic individuals with open angles underwent anterior segment OCT imaging under 3 pupillary states: (1) pupil constricted under standard room lighting, (2) physiologic mydriasis in a darkened room, and (3) postpharmacologic mydriasis. Inferior angle Schwalbe’s line-angle opening distance (SL-AOD) and SL-trabecular-iris-space area (SL-TISA) were computed for each eye and pupillary condition by masked, certified Reading Center graders using customized grading software. Results. SL-AOD and SL-TISA under pupillary constriction to room light were 0.87±0.31 mm and 0.33±0.14 mm2, respectively; decreased to 0.75±0.29 mm P