Abstract
Purpose :
Up to 50% of patients with prion disease develop visual symptoms including loss of visual acuity, visual field defects, micropsia, macropsia, metamorphopsia, palinopsia, and dyschromatopsia. Visual symptoms can precede neurological symptoms, making the diagnosis a challenge. Studies have revealed the presence of PrP deposits in the retinas of patients with sCJD. However, the molecular and morphologic characteristics of retinal PrP deposits are unknown. Here, we performed quantitative assessments of retinal PrP deposits from 14 clinically documented sCJD cases in the largest series of documented prion cases to date.
Methods :
From December 2015 to May 2017, 28 eyes were collected from 14 autopsies of clinically suspected prion disease and 6 of non-prion controls. sCJD was confirmed concomitantly by brain autopsy. Immunohistochemistry was performed with antibodies against PrP and deposition within the retina was evaluated by microscopy. We performed histologic and morphologic analysis on 202 retinal PrP deposits across 14 sCJD cases. Statistical significance was evaluated using an unpaired t-test and Mann-Whitney test.
Results :
In all fourteen CJD cases, PrP deposits were observed in the retina as round aggregates confined to the inner and outer plexiform layers. The deposits formed thin layers, possibly at a layer of synapses, in CJD cases. No retinal deposits were observed in control normal eyes. PrP deposits in the retina are small (5.02 um +/- 0.50). The retinal deposits showed consistent globular morphology and were not associated with retinal spongiosis or degeneration.
Conclusions :
PrP deposits are a consistent finding in the retinas of patients with prion disease. Interestingly, they show completely different morphology compared to brain PrP deposits. The retinal prion deposits are localized in discrete round aggregates predominantly in the outer plexiform layer. Retinal PrP deposits are not linked to obvious retinal cell death or spongiform changes within the neuroretina, in contrast to the severe spongiotic neurodegeneration induced by brain PrP deposits. We speculate that these PrP deposits underlie the visual symptoms commonly reported by prion disease patients. Retinal imaging in clinically suspected prion disease could display abnormalities similar to those in histologic sections.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.