Optical coherence tomography measurements as potential imaging biomarkers for Parkinson's disease: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Retinal pathological changes may precede or accompany the deterioration of brain tissue in Parkinson's disease (PD). The purpose of this meta-analysis was to assess the usefulness of optical coherence tomography (OCT) measurements as potential imaging biomarkers for PD. METHODS: PubMed, Embase, Web of Science and Cochrane Library databases were systematically searched for observational studies (published prior to 30 May 2020) comparing the OCT measurements between PD patients and healthy controls (HCs). Our main end-points were peripapillary retinal nerve fiber layer (pRNFL) thickness, macular ganglion cell complex thickness, macular thickness and macular volume. Pooled data were assessed by use of a random-effects model. RESULTS: A total of 36 observational studies were identified that included 1712 patients with PD (2548 eyes) and 1778 HCs (2646 eyes). Compared with the HC group, the PD group showed a significant reduction in mean pRNFL thickness (weighted mean difference [WMD] -3.51 µm, 95% confidence interval [CI] -4.84, -2.18; p = 0.000), all quadrants at the pRNFL (WMD range -7.65 to -2.44 µm, all p < 0.05), macular fovea thickness (WMD -5.62 µm, 95% CI -7.37, -3.87; p = 0.000), all outer sector thicknesses at the macula (WMD range -4.68 to -4.10 µm, all p < 0.05), macular volume (WMD -0.21 mm3 , 95% CI -0.36, -0.06; p < 0.05) and macular ganglion cell complex thickness (WMD -4.18 µm, 95% CI -6.07, -2.29; p < 0.05). CONCLUSIONS: Our pooled data confirmed robust associations between retinal OCT measurements and PD, highlighting the usefulness of OCT measurements as potential imaging biomarkers for PD.

Mitochondria as Potential Targets and Initiators of the Blue Light Hazard to the Retina.

Commercially available white light-emitting diodes (LEDs) have an intense emission in the range of blue light, which has raised a range of public concerns about their potential risks as retinal hazards. Distinct from other visible light components, blue light is characterized by short wavelength, high energy, and strong penetration that can reach the retina with relatively little loss in damage potential. Mitochondria are abundant in retinal tissues, giving them relatively high access to blue light, and chromophores, which are enriched in the retina, have many mitochondria able to absorb blue light and induce photochemical effects. Therefore, excessive exposure of the retina to blue light tends to cause ROS accumulation and oxidative stress, which affect the structure and function of the retinal mitochondria and trigger mitochondria-involved death signaling pathways. In this review, we highlight the essential roles of mitochondria in blue light-induced photochemical damage and programmed cell death in the retina, indicate directions for future research and preventive targets in terms of the blue light hazard to the retina, and suggest applying LED devices in a rational way to prevent the blue light hazard.

Mitochondrial Fission Is Required for Blue Light-Induced Apoptosis and Mitophagy in Retinal Neuronal R28 Cells.

Light emitting diodes (LEDs) are widely used to provide illumination due to their low energy requirements and high brightness. However, the LED spectrum contains an intense blue light component which is phototoxic to the retina. Recently, it has been reported that blue light may directly impinge on mitochondrial function in retinal ganglion cells (RGCs). Mitochondria are high dynamic organelles that undergo frequent fission and fusion events. The aim of our study was to elucidate the role of mitochondrial dynamics in blue light-induced damage in retinal neuronal R28 cells. We found that exposure to blue light (450 nm, 1000 lx) for up to 12 h significantly up-regulated the expression of mitochondrial fission protein Drp1, while down-regulating the expression of mitochondrial fusion protein Mfn2 in cells. Mitochondrial fission was simultaneously stimulated by blue light irradiation. In addition, exposure to blue light increased the production of reactive oxygen species (ROS), disrupted mitochondrial membrane potential (MMP), and induced apoptosis in R28 cells. Notably, Drp1 inhibitor Mdivi-1 and Drp1 RNAi not only attenuated blue light-induced mitochondrial fission, but also alleviated blue light-induced ROS production, MMP disruption and apoptosis in cells. Compared with Mdivi-1 and Drp1 RNAi, the antioxidant N-acetyl-L-cysteine (NAC) only slightly inhibited mitochondrial fission, while significantly alleviating apoptosis after blue light exposure. Moreover, we examined markers for mitophagy, which is responsible for the clearance of dysfunctional mitochondria. It was found that blue light stimulated the conversion of LC3B-I to LC3B-II as well as the expression of PINK1 in R28 cells. Mdivi-1 or Drp1 RNAi efficiently inhibited the blue light-induced expression of PINK1 and co-localization of LC3 with mitochondria. Thus, our data suggest that mitochondrial fission is required for blue light-induced mitochondrial dysfunction and apoptosis in RGCs.