They concluded, “Our study revealed defective calcium clearance as a signature feature of early RGC damage, a trait conserved across RGC subtypes, and suggested that loss of SERCA2 has a profoundly detrimental effect on the ability of these neurons to regulate cytoplasmic calcium. In contrast, the investigators noted, the glaucomatous eyes treated with a SERCA2-specific activator restored the ability of RGCs to effectively reduce cytoplasmic calcium to physiologic levels. The recordings in naïve mice treated with a pharmacologic inhibitor of SERCA2 showed impaired calcium clearance in the RGCs, recapitulating the ocular hypertensive effects. This reduced gene and protein expression in the ER was accompanied by up-regulated ER stress markers pPERK, pEIF-2a, ATF4, and CHOP. They explained that when they analyzed the molecular pathways, they observed an “RGC-specific reduction in gene and protein expression of the endoplasmic reticulum (ER) calcium ATPase 2 (SERCS2),” which pumps calcium from the cytoplasm to the ER. They found, for example, that optic nerve RGCs that were subjected to ocular hypertension had a significantly (p<0.01) increased calcium decay time compared to sham controls, that is, 2.8 seconds versus 1.1 seconds, respectively. In this study, the researchers reported that trans-scleral imaging in the live mice and ex vivo imaging showed significant consistent defects in calcium clearance in all RGC types. 15 Several experimental studies have indicated that RGC apoptosis occurs in the ganglion. The parameters studied were the calcium influx and clearance times and amplitude, the investigators described. The human retina contains 1.5 million RGCs, which are not confined to 1 of the 10 distinct retinal layers. Two-photon laser scanning microscopy recorded the light-evoked RGC calcium dynamics in the living transgenic mice and later in the retinal explants. The calcium signals were recorded 2 weeks later before loss of the RGCs. In this mouse model, ocular hypertension developed with the intracameral injection of magnetic microbeads. They hypothesized that RGC calcium dynamics are affected in early-stage ocular hypertension. He and his research team conducted this experimental mouse study to determine the mechanisms that cause RGC vulnerability. Shiga is the lead author of the study from the Neuroscience departments of the Centre Hospitalier de l'Universite de Montreal Centre de Recherche, and the Universite de Montreal, Montreal, Quebec, Canada. Yukihiro Shiga, MD, reported that defective calcium clearance is a characteristic feature of early damage to the retinal ganglion cells (RGC) in a mouse model of glaucoma. Retinal ganglion cell (RGC) loss is the hallmark of optic neuropathies, including glaucoma, where damage to RGC axons occurs at the level of the optic nerve head. To estimate retinal ganglion cell (RGC) losses associated with a relative afferent pupillary defect (RAPD) in glaucoma.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |