Oxidative stress-induced cellular senescence in aging retina and age-related macular degeneration

Aging leads to a gradual decline of function in multiple organs. Cataract, glaucoma, diabetic retinopathy, and age-related macular degeneration (AMD) are age-related ocular diseases. Because their pathogenesis is unclear, it is challenging to combat age-related diseases. Cellular senescence is a cellular response characterized by cell cycle arrest. Cellular senescence is an important contributor to aging and age-related diseases through the alteration of cellular function and the secretion of senescence-associated secretory phenotypes. As a driver of stress-induced premature senescence, oxidative stress triggers cellular senescence and age-related diseases by inducing senescence markers via reactive oxygen species and mitochondrial dysfunction. In this review, we focused on the mechanism of oxidative stress-induced senescence in retinal cells and its role in the pathogenesis of AMD

Identification of Autoantibodies against TRPM1 in Patients with Paraneoplastic Retinopathy Associated with ON Bipolar Cell Dysfunction

Background: Paraneoplastic retinopathy (PR), including cancer-associated retinopathy (CAR) and melanoma-associated retinopathy (MAR), is a progressive retinal disease caused by antibodies generated against neoplasms not associated with the eye. While several autoantibodies against retinal antigens have been identified, there has been no known autoantibody reacting specifically against bipolar cell antigens in the sera of patients with PR. We previously reported that the transient receptor potential cation channel, subfamily M, member 1 (TRPM1) is specifically expressed in retinal ON bipolar cells and functions as a component of ON bipolar cell transduction channels. In addition, this and other groups have reported that human TRPM1 mutations are associated with the complete form of congenital stationary night blindness. The purpose of the current study is to investigate whether there are autoantibodies against TRPM1 in the sera of PR patients exhibiting ON bipolar cell dysfunction. Methodology/Principal Findings: We performed Western blot analysis to identify an autoantibody against TRPM1 in the serum of a patient with lung CAR. The electroretinograms of this patient showed a severely reduced ON response wit

Changes in pulse waveforms in response to intraocular pressure elevation determined by laser speckle flowgraphy in healthy subjects

Background: The influences of intraocular pressure (IOP) elevations on the pulse waveform in the optic nerve head (ONH) were evaluated using laser speckle flowgraphy (LSFG) in normal subjects. Methods: This prospective cross-sectional study was conducted at the Nagoya University Hospital. An ophthalmodynamometer was pressed on the sclera to increase the IOP by 20 mmHg or 30 mmHg for 1 min (experiment 1, 16 subjects) and by 30 mmHg for 10 min (experiment 2, 10 subjects). The mean blur rate (MBR) and the eight pulse waveform parameters determined using LSFG were measured before, immediately after and during an IOP elevation, and after the IOP returned to the baseline pressure. Results: A significant elevation in the IOP and a significant reduction in the ocular perfusion pressure (OPP) were found after applying the ophthalmodynamometer (both, P < 0.001). The blowout score (BOS) reduced significantly (P < 0.001), and the flow acceleration index (FAI; P < 0.01) and resistivity index (RI; P < 0.001) increased significantly immediately after increasing the IOP by 20 or 30 mmHg (experiment 1). The BOS reduced significantly (P < 0.001), and the FAI (P < 0.01) and RI (P < 0.001) increased significantly after the IOP elevation by 30 mmHg in both experiment 2 and 1. However, the BOS and RI recovered significantly at time 10 compared to that in time 0 (immediately after IOP elevation) during the 10-min IOP elevation (P < 0.001 and P = 0.008, respectively). Conclusions: In conclusion, the BOS, FAI, and RI of the pulse waveforms changed significantly with an acute elevation in the IOP. The change should be related to the larger difference between the maximum and minimum MBRs during the IOP elevation