Purpose
Ophthalmic complications are quite common in patients suffered from Parkinson’s disease (PD) and Alzheimer’s disease (AD). In this pilot study, we investigated key proteins involved in PD and AD pathogenesis in human eyes. Specifically, Alpha-synuclein (α-syn) and DJ-1, mutation of which cause autosomal dominant and autosomal recessive PD, respectively, as well as tau and amyloid β (Aβ), i.e. proteins critical to AD pathogenesis, are targeted in the study, with the hope that alterations associated with PD and or AD proteins can be indented in eyes, thereby providing a window by which pathological alterations in the central nervous system can be probed readily and noninvasively.
Methods
Fresh human globes were collected at autopsy using approved IRB protocol. A total of 11 cases were included in the investigation: PD (5 lens / 3 individuals), AD (8 lens / 4 individuals) and healthy controls (7 lens / 4 individuals). The globes were dissected and the ocular tissues were separated for further analysis by immunohistochemistry, immunoprecipitation, Western blotting and mass spectrometry.
Results
All four key biomarkers, α-syn, DJ-1, Tau and Aβ were identified in various areas of human globes. For example, α-syn was well detectable in the retina (Fig 1), whereas DJ-1 was seen in almost all parts of eye globe, including lens material. The expression of these proteins in eye can be quite significant. For instance, because DJ-1 is an antioxidative protein, it might contribute to cataract formation, in addition to its potential role of indicating PD process via eyes.
Conclusions
Four key biomarkers involved in PD and AD pathogenesis, α-syn, DJ-1, Tau and Aβ were present in human ocular tissue. This provides a prospect to detect pathological alterations in the central nervous system noninvasively and earlier.