Abstract
Purpose :
Transmissible ‘scrapie-type’ prion (PrPSc) deposits have been detected in the retina of patients with sporadic Creutzfeldt-Jakob disease (sCJD); however, the histopathology of retinal PrPSc deposits is poorly characterized, whereas that in the brain is well established. We performed a retrospective, observational study to characterize the morphometric features of PrPSc deposits and the histological changes in the retinas of patients with sCJD.
Methods :
From July 2015 to July 2017, 14 eyes and 1 brain were collected from 14 neuropathologically-confirmed sCJD autopsy cases (4 males and 10 females; age range: 51-80, mean: 63, SD: 9.0; disease duration: 1.5-27 mo, mean: 10.5, SD: 8.4) and eyes and brains from 6 controls (5 males and 1 female; age range: 51-90, mean: 70.3, SD: 13.8). Immunohistochemistry was performed with Mab12F10 (Cayman Chemical; 1:200) against PrPSc. The greatest dimension of PrPSc staining was microscopically measured and statistical significance was evaluated with Mann-Whitney U test, Welch’s unpaired t-test, and Brown-Forsythe test.
Results :
PrPSc expression was found in the outer (OPL) and inner plexiform layers (IPL) of the retinas with the strongest deposition as discrete, regularly spaced ovoid deposits in a “beads-on-a-string” pattern along the horizontal axis of the OPL. PrPSc deposits were not observed in controls nor other ocular structures of the patient group. The average size of retinal PrPSc deposits in the OPL was 4.94µm, which was significantly smaller than coarse PrPSc deposits in the brain (32.45µm, p<0.001) with a significantly lower SD (0.47µm vs. 23.55µm, p<0.001). Retinal lamination and laminar thickness were comparable between sCJD retinas and controls. Spongiotic changes and overt gliosis were not observed in the retinas with PrPSc deposition.
Conclusions :
Our findings show that PrPSc deposits in the retina have significantly different histologic and morphometric characteristics than those in the brain. Retinal PrPSc deposits are consistently present in ovoid aggregates in the OPL with a relatively uniform size of 5 µm. In contrast to the spongiform neurodegeneration associated with PrPScdeposition in the brain, retinal anatomy and organization appear well-preserved despite PrPSc deposition in OPL. Additional studies are required to determine the cellular location and function of PrPSc deposits in OPL.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.