Loss of Fas Receptor Function Preserves Photoreceptor Structure and Function in Two Mouse Models of Inherited Retinal Degeneration.

Purpose: The genetic heterogeneity of inherited retinal degeneration (IRD) has limited the development of mutation-specific therapies, necessitating the development of therapeutic approaches targeting broadly shared pathophysiologic pathways. The Fas receptor has been reported as a contributor to retinal cell death and inflammation in a wide variety of ocular diseases. The purpose of this study was to assess targeting the Fas pathway as a novel mutation-independent approach to improve photoreceptor survival in IRD.

Correlation of vascular change and cognitive impairment in age-related macular degeneration patients.

Age-related macular degeneration (AMD) is one of the leading causes of blindness among the elderly. However, the correlation between vascular change and cognitive impairment in AMD disease is still unknown. In our study, we investigate the blood flow change among different layers of the retina in the AMD eye and normal fellow eye of AMD patients and its influence with patients' cognition.

Shifting the balance of autophagy and proteasome activation reduces proteotoxic cell death: a novel therapeutic approach for restoring photoreceptor homeostasis.

The P23H variant of rhodopsin results in misfolding of the protein, and is a common cause of the blinding disease autosomal dominant retinitis pigmentosa (adRP). We have recently demonstrated that degeneration of photoreceptor cells in retinas of P23H mice is due to the endoplasmic reticulum stress (ERS)-induced activation of autophagy that leads to a secondary proteasome insufficiency and activation of cell death pathways. We propose that this increased level of autophagy flux relative to proteasome activity, which we term the A:P ratio, represents a marker of altered photoreceptor cell homeostasis, and that therapies aimed at normalizing this ratio will result in increased photoreceptor cell survival.

Autophagosome immunoisolation from GFP-LC3B mouse tissue.

We describe a protocol for rapid and efficient enrichment of autophagosomes from various tissues of the GFP-LC3 mouse. In order to increase the number of autophagosomes, we block autophagy flux in the GFP-LC3 mouse tissue with a single intraperitoneal injection of leupeptin 4-5 h before tissue harvesting. We homogenize dissected tissue samples using a Dounce homogenizer followed by passing the slurry through needles of different sizes to dissociate the cells and disrupt their outer membranes.

Inhibiting autophagy reduces retinal degeneration caused by protein misfolding.

Mutations in the genes necessary for the structure and function of vertebrate photoreceptor cells are associated with multiple forms of inherited retinal degeneration. Mutations in the gene encoding RHO (rhodopsin) are a common cause of autosomal dominant retinitis pigmentosa (adRP), with the Pro23His variant of RHO resulting in a misfolded protein that activates endoplasmic reticulum stress and the unfolded protein response. Stimulating macroautophagy/autophagy has been proposed as a strategy for clearing misfolded RHO and reducing photoreceptor death.

Problem/case-based learning with competition introduced in severe infection education: an exploratory study.

Background: Problem/case-based learning (PCBL) is one of the most commonly used educational methods in medical schools.

Aim: To further improve PCBL in clinical course of severe infection by introducing competition mode.

Methods: Two classes of medical students were divided into two groups by class-based simple randomization and were taught the course of severe infection by PCBL.