Purpose: To examine the expression and cellular distribution pattern of endothelial nitric oxide synthase (eNOS) in the developing human retina and to compare its expression with that in rats.
Methods: Expression of eNOS was examined by immunohistochemistry in retinas of humans ranging from 8.5 to 28 weeks of gestation (WG) and of rats.
Results: In the developing human retina, eNOS expression was first detected in the proximal margin of the neuroblastic layer in the incipient fovea-surrounding area at 12 WG. At 17 to 28 WG, eNOS-immunoreactive cells were located in the innermost part of the inner nuclear layer and in the ganglion cell layer, expanding to both temporal and nasal retinas and the processes projecting into the inner plexiform layer. These eNOS-positive cells coexpressed syntaxin and glutamate decarboxylase, and are probably GABAergic amacrine cells. The onset of eNOS expression in developing amacrine cells, however, preceded the invasion of retinal vasculature, long before vascular function involving these cells can be expected, suggesting that eNOS has a role not only in vasoregulation but also in retinal development. From 20 WG on, eNOS was also detected in the photoreceptors adjacent to the fovea. eNOS expression in amacrine cells and photoreceptors was observed in the central-to-peripheral and temporal-to-nasal gradients. However, in the developing rat retina, eNOS was expressed exclusively in the vascular endothelial cells.
Conclusions: The results support that eNOS plays a role, not only in the regulation of vascular function but also in the process of retinal development in humans.
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http://dx.doi.org/10.1167/iovs.04-1202 | DOI Listing |
D e h ydro d olichyl d iphosphate s ynthase (DHDDS) is an essential enzyme required for several forms of protein glycosylation in all eukaryotic cells. Surprisingly, three mutant alleles, ( (K42E/K42E), (T206A/K42E), and found in only one patient, (R98W/K42E) have been reported that cause non-syndromic retinitis pigmentosa (RP59), an inherited retinal degeneration (IRD). Because T206A was only observed heterozygously with the K42E allele in RP59 patients, we used CRISPR/CAS9 technology to generate T206A/T206A, and subsequently T206A/K42E alleles in mice to assess the contribution of the T206A allele to the disease phenotype, to model the human disease, and to compare resulting phenotypes to our homozygous K42E mouse model.
View Article and Find Full Text PDFBrain Stimul
January 2025
Graduate School of Biomedical Engineering, UNSW, Sydney, NSW 2052, Australia; Tyree Foundation Institute of Health Engineering (IHealthE), UNSW, Sydney, NSW 2052, Australia. Electronic address:
Introduction: Current brain-based visual prostheses pose significant challenges impeding adoption such as the necessarily complex surgeries and occurrence of more substantial side effects due to the sensitivity of the brain. This has led to much effort toward vision restoration being focused on the more approachable part of the brain - the retina. Here we introduce a novel, parameterized simulation platform that enables study of human retinal degeneration and optimization of stimulation strategies.
View Article and Find Full Text PDFBio Protoc
January 2025
Department of Biomedicine, University of Bergen, Bergen, Norway.
During neuronal synaptic transmission, the exocytotic release of neurotransmitters from synaptic vesicles in the presynaptic neuron evokes a change in conductance for one or more types of ligand-gated ion channels in the postsynaptic neuron. The standard method of investigation uses electrophysiological recordings of the postsynaptic response. However, electrophysiological recordings can directly quantify the presynaptic release of neurotransmitters with high temporal resolution by measuring the membrane capacitance before and after exocytosis, as fusion of the membrane of presynaptic vesicles with the plasma membrane increases the total capacitance.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Brain Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
Retinal ganglion cells (RGCs) typically respond to light stimulation over their spatially restricted receptive field. Using large-scale recordings in the mouse retina, we show that a subset of non- direction-selective (DS) RGCs exhibit asymmetric activity, selective to motion direction, in response to a stimulus crossing an area far beyond the classic receptive field. The extraclassical response arises via inputs from an asymmetric distal zone and is enhanced by desensitization mechanisms and an inherent DS component, creating a network of neurons responding to motion toward the optic disc.
View Article and Find Full Text PDFThis study characterizes a fluorescent -tdTomato neuronal reporter mouse line with strong labeling of axons throughout the optic nerve, of retinal ganglion cell (RGC) soma in the ganglion cell layer (GCL), and of RGC dendrites in the inner plexiform layer (IPL). The model facilitated assessment of RGC loss in models of degeneration and of RGC detection in mixed neural/glial cultures. The tdTomato signal showed strong overlap with >98% cells immunolabeled with RGC markers RBPMS or BRN3A, consistent with the ubiquitous presence of the vesicular glutamate transporter 2 (VGUT2, SLC17A6) in all RGC subtypes.
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