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Human photoreceptor cells from different macular subregions have distinct transcriptional profiles

Thu, 2021-05-20 05:00

Hum Mol Genet. 2021 May 20:ddab140. doi: 10.1093/hmg/ddab140. Online ahead of print.


The human neural retina is a light sensitive tissue with remarkable spatial and cellular organization. Compared to the periphery, the central retina contains more densely packed cone photoreceptor cells with unique morphologies and synaptic wiring. Some regions of the central retina exhibit selective degeneration or preservation in response to retinal disease and the basis for this variation is unknown. In this study, we used both bulk and single-cell RNA sequencing to compare gene expression within concentric regions of the central retina. We identified unique gene expression patterns of foveal cone photoreceptor cells, including many foveal-enriched transcription factors. In addition, we found that the genes RORB1, PPFIA1, and KCNAB2 are differentially spliced in the foveal, parafoveal, and macular regions. These results provide a highly detailed spatial characterization of the retinal transcriptome and highlight unique molecular features of different retinal regions.

PMID:34014299 | DOI:10.1093/hmg/ddab140

Practice Diversity and Burn Center Growth: A 10-Year Profile of a State's Only Burn Center

Tue, 2021-05-18 05:00

Ann Plast Surg. 2021 Jun 1;86(4S Suppl 4):S452-S453. doi: 10.1097/SAP.0000000000002787.


BACKGROUND: Growth and sustainability of burn practices can be impaired by irregular patterns of patient presentations, resulting in uneven utilization of facilities and staff. Burn care itself may not engage the full capacities of members of burn care teams. To address these problems, we organized a burn and reconstruction center to provide statewide acute care as Mississippi's only burn unit, to fully integrate reconstructive surgery into management of burn patients, and to diversify practice based on plastic surgery scope of practice. The first 10 years of this unit were reviewed to evaluate the performance of this scheme.

METHODS: Burn admissions to and surgical procedures at this unit between July 2009 and June 2019 were analyzed to quantify acute burn care, secondary reconstructive burn care, and categories of practice growth.

RESULTS: The unit admitted 5469 acute burn patients with a mortality rate of 1.49%. Comparing year 10 to year 1 of practice, acute burn admissions increased 58%. Total operations increased 276%. Acute burn procedures increased 176%. Secondary burn procedures increased 405%. Nonburn procedures increased 352%, with the subset of nonburn hand surgery increasing 1062%.

CONCLUSION: Acute burn admissions and procedures increased over this period, but greater growth was seen in secondary burn procedures and nonburn procedures, especially hand cases. Expansion of practice into areas within the overall skill sets of burn team members was an effective growth strategy.

PMID:34002719 | DOI:10.1097/SAP.0000000000002787

Cell-Matrix Interactions in the Eye: From Cornea to Choroid

Sat, 2021-04-03 05:00

Cells. 2021 Mar 20;10(3):687. doi: 10.3390/cells10030687.


The extracellular matrix (ECM) plays a crucial role in all parts of the eye, from maintaining clarity and hydration of the cornea and vitreous to regulating angiogenesis, intraocular pressure maintenance, and vascular signaling. This review focuses on the interactions of the ECM for homeostasis of normal physiologic functions of the cornea, vitreous, retina, retinal pigment epithelium, Bruch's membrane, and choroid as well as trabecular meshwork, optic nerve, conjunctiva and tenon's layer as it relates to glaucoma. A variety of pathways and key factors related to ECM in the eye are discussed, including but not limited to those related to transforming growth factor-β, vascular endothelial growth factor, basic-fibroblastic growth factor, connective tissue growth factor, matrix metalloproteinases (including MMP-2 and MMP-9, and MMP-14), collagen IV, fibronectin, elastin, canonical signaling, integrins, and endothelial morphogenesis consistent of cellular activation-tubulogenesis and cellular differentiation-stabilization. Alterations contributing to disease states such as wound healing, diabetes-related complications, Fuchs endothelial corneal dystrophy, angiogenesis, fibrosis, age-related macular degeneration, retinal detachment, and posteriorly inserted vitreous base are also reviewed.

PMID:33804633 | PMC:PMC8003714 | DOI:10.3390/cells10030687

The SWELL1-LRRC8 complex regulates endothelial AKT-eNOS signaling and vascular function

Thu, 2021-02-25 05:00

Elife. 2021 Feb 25;10:e61313. doi: 10.7554/eLife.61313. Online ahead of print.


The endothelium responds to numerous chemical and mechanical factors in regulating vascular tone, blood pressure and blood flow. The endothelial volume regulatory anion channel (VRAC) has been proposed to be mechano-sensitive and thereby sense fluid flow and hydrostatic pressure to regulate vascular function. Here, we show that the Leucine Rich Repeat Containing Protein 8a, LRRC8A (SWELL1) is required for VRAC in human umbilical vein endothelial cells (HUVECs). Endothelial LRRC8A regulates AKT-eNOS signaling under basal, stretch and shear-flow stimulation, forms a GRB2-Cav1-eNOS signaling complex, and is required for endothelial cell alignment to laminar shear flow. Endothelium-restricted Lrrc8a KO mice develop hypertension in response to chronic angiotensin-II infusion and exhibit impaired retinal blood flow with both diffuse and focal blood vessel narrowing in the setting of Type 2 diabetes (T2D). These data demonstrate that LRRC8A regulates AKT-eNOS in endothelium and is required for maintaining vascular function, particularly in the setting of T2D.

PMID:33629656 | DOI:10.7554/eLife.61313