Phosphorylated α-synuclein-immunoreactive retinal neuronal elements in Parkinson's disease subjects

Visual symptoms are relatively common in Parkinson's disease (PD) and optical coherence tomography has indicated possible retinal thinning. Accumulation of aggregated α-synuclein is thought to be a central pathogenic event in the PD brain but there have not as yet been reports of retinal synucleinopathy. Retinal wholemounts were prepared from subjects with a primary clinicopathological diagnosis of PD (N = 9), dementia with Lewy bodies (DLB; N = 3), Alzheimer's disease (N = 3), progressive supranuclear palsy (N = 2) as well as elderly normal control subjects (N = 4). These were immunohistochemically stained with an antibody against α-synuclein phosphorylated at serine 129, which is a specific molecular marker of synucleinopathy. Phosphorylated α-synuclein-immunoreactive (p-syn IR) nerve fibers were present in 7/9 PD subjects and in 1/3 DLB subjects; these were sparsely distributed and superficially located near or at the inner retinal surface. The fibers were either long and straight or branching, often with multiple en-passant varicosities along their length. The straight fibers most often had an orientation that was radial with respect to the optic disk. Together, these features are suggestive of either retinopetal/centrifugal fibers or of ganglion cell axons. In one PD subject there were sparse p-syn IR neuronal cell bodies with dendritic morphology suggestive of G19 retinal ganglion cells or intrinsically photosensitive ganglion cells. There were no stained nerve fibers or other specific staining in any of the non-PD or non-DLB subjects. It is possible that at least some of the observed visual function impairments in PD subjects might be due to α-synucleinopathy.

Calcineurin expression and activity is regulated by the intracellular redox status and under hypertension in human neutrophils

Calcineurin (protein phosphatase 2B) (CN) comprises a family of serine/threonine phosphatases that play a pivotal role in signal transduction cascades in a variety of cells, including neutrophils. Angiotensin II (Ang II) increases both activity and de novo synthesis of CN in human neutrophils. This study focuses on the role that intracellular redox status plays in the induction of CN activity by Ang II. Both de novo synthesis of CN and activity increase promoted by Ang II were downregulated when cells were treated with l-buthionine-(S,R)-sulfoximine, an inhibitor of synthesis of the antioxidant glutathione. We have also investigated the effect of pyrrolidine dithiocarbamate and phenazine methosulfate, which are antioxidant and oxidant compounds, respectively, and concluded that the intracellular redox status of neutrophils is highly critical for Ang II-induced increase of CN expression and activity. Results obtained in neutrophils from hypertensive patients were very similar to those obtained in these cells on treatment with Ang II. We have also addressed the possible functional implication of CN activation in the development of hypertension. Present findings indicate that downregulation of hemoxygenase-1 expression in neutrophils from hypertensive subjects is likely mediated by CN, which acts by hindering translocation to the nucleus of the transcription factor NRF2. These data support and extend our previous results and those from other authors on modulation of CN expression and activity levels by the intracellular redox status.

Correlation of the Corneal Toricity Between Anterior and Posterior Corneal Surfaces in the Normal Human Eye

Purpose: To evaluate the correlation of the magnitude of corneal toricity and power vector components of both corneal surfaces measured with a Scheimpflug photography-based system. Methods: A total of 117 healthy normal eyes of 117 subjects selected randomly with ages ranging from 7 to 80 years were included. All eyes received an anterior segment and corneal analysis with the Sirius system (CSO) evaluating the anterior and posterior mean toricity for 3 and 7 mm (aAST and pAST). The vector components J0 and J45 as well as the overall strength blur (B) were calculated for each keratometric measurement using the procedure defined by Thibos and Horner. Results: The coefficient of correlation between aAST and pAST was 0.52 and 0.62 and the mean anteroposterior ratio for toricity was 0.46 ± 0.39 and 0.57 ± 0.75 for 3 and 7 mm, respectively. These ratios correlated significantly with aAST, anterior corneal J0, and manifest refraction J0 (r ≥ 0.39, P < 0.01). The coefficient of correlation was 0.69 and 0.81 between anterior and posterior J0 for 3 and 7 mm, respectively. For J45, the coefficients were 0.62 and 0.71, respectively. The linear regression analysis revealed that the pAST and power vectors could be predicted from the anterior corneal data (R2 ≥ 0.40, P < 0.01). Conclusions: The toricity and astigmatic power vector components of the posterior corneal surface in the human healthy eye are related to those of the anterior and therefore can be predicted consistently from the anterior toricity and astigmatic power vectors.