scholarly journals Visual Disfunction due to the Selective Effect of Glutamate Agonists on Retinal Cells

2021 ◽  
Vol 22 (12) ◽  
pp. 6245
Author(s):  
Santiago Milla-Navarro ◽  
Ariadna Diaz-Tahoces ◽  
Isabel Ortuño-Lizarán ◽  
Eduardo Fernández ◽  
Nicolás Cuenca ◽  
...  

One of the causes of nervous system degeneration is an excess of glutamate released upon several diseases. Glutamate analogs, like N-methyl-DL-aspartate (NMDA) and kainic acid (KA), have been shown to induce experimental retinal neurotoxicity. Previous results have shown that NMDA/KA neurotoxicity induces significant changes in the full field electroretinogram response, a thinning on the inner retinal layers, and retinal ganglion cell death. However, not all types of retinal neurons experience the same degree of injury in response to the excitotoxic stimulus. The goal of the present work is to address the effect of intraocular injection of different doses of NMDA/KA on the structure and function of several types of retinal cells and their functionality. To globally analyze the effect of glutamate receptor activation in the retina after the intraocular injection of excitotoxic agents, a combination of histological, electrophysiological, and functional tools has been employed to assess the changes in the retinal structure and function. Retinal excitotoxicity caused by the intraocular injection of a mixture of NMDA/KA causes a harmful effect characterized by a great loss of bipolar, amacrine, and retinal ganglion cells, as well as the degeneration of the inner retina. This process leads to a loss of retinal cell functionality characterized by an impairment of light sensitivity and visual acuity, with a strong effect on the retinal OFF pathway. The structural and functional injury suffered by the retina suggests the importance of the glutamate receptors expressed by different types of retinal cells. The effect of glutamate agonists on the OFF pathway represents one of the main findings of the study, as the evaluation of the retinal lesions caused by excitotoxicity could be specifically explored using tests that evaluate the OFF pathway.

1994 ◽  
Vol 269 (4) ◽  
pp. 2943-2952
Author(s):  
L.F. Brass ◽  
S. Pizarro ◽  
M. Ahuja ◽  
E. Belmonte ◽  
N. Blanchard ◽  
...  

Gene Therapy ◽  
2021 ◽  
Author(s):  
Shagana Visuvanathan ◽  
Adam N. Baker ◽  
Pamela S. Lagali ◽  
Stuart G. Coupland ◽  
Garfield Miller ◽  
...  

2020 ◽  
Vol 35 (6) ◽  
pp. 895-895
Author(s):  
Demmin D ◽  
Klein S ◽  
Silverstein S

Abstract Objective The retina may provide a unique window into brain structure and function as an accessible part of the central nervous system. Abnormalities in retinal cell structure and function have been associated with brain pathology (e.g., brain volume loss, cognitive impairment) in several neuropsychiatric disorders (e.g., MS, Alzheimer’s disease, Parkinson’s disease). A number of prior studies using flash electroretinography (fERG) have reported reduced retinal cell activity in schizophrenia (SZ). Impairments in cognitive functioning are a core feature of SZ and deficits in executive control processes involving prefrontal cortex (PFC) activity are strong predictors of functional capacity. This study examined whether retinal cell functioning is related to brain function, as indexed by cognitive function, in SZ, and if these relationships were stronger in particular domains (e.g., PFC dependent functions vs. less PFC dependent functions). Method Twenty-six SZ participants and 24 healthy controls (HC) completed fERG and cognitive testing. fERG measurements included a-wave (photoreceptor cells), b-wave (bipolar-Müller cells), and oscillatory potential (OP; amacrine cells) amplitudes and implicit times. Cognitive tests assessed executive control processes (i.e., attention/processing speed, behavior initiation, response inhibition, working memory), and non-executive control processes (i.e., emotion recognition/discrimination). Results In the HC group, a-wave amplitude was correlated with cognitive test scores and OP amplitude was related to cognitive performance in the SZ group. However, overall, retinal cell activity did not appear to be strongly related to scores on cognitive tasks, regardless of whether or not they involved frontal brain regions. Conclusion Impairments in retinal and cognitive functioning may reflect distinct disease mechanisms in schizophrenia.


2011 ◽  
Vol 211 (1) ◽  
pp. 3-16 ◽  
Author(s):  
Gavin P Vinson

Over the 70 or so years since their discovery, there has been continuous interest and activity in the field of corticosteroid functions. However, despite major advances in the characterisation of receptors and coregulators, in some ways we still lack clear insight into the mechanism of receptor activation, and, in particular, the relationship between steroid hormone structure and function remains obscure. Thus, why should deoxycorticosterone (DOC) reportedly be a weak mineralocorticoid, while the addition of an 11β-hydroxyl group produces glucocorticoid activity, yet further hydroxylation at C18 leads to the most potent mineralocorticoid, aldosterone? This review aims to show that the field has been confused by the misreading of the earlier literature and that DOC, far from being relatively inactive, in fact has a wide range of activities not shared by the other corticoids. In contrast to the accepted view, the presence of an 11β-hydroxyl group yields, in corticosterone or cortisol, hormones with more limited functions, and also more readily regulated, by 11β-hydroxysteroid dehydrogenase. This interpretation leads to a more systematic understanding of structure–function relationships in the corticosteroids and may assist more rational drug design.


2014 ◽  
Vol 55 (11) ◽  
pp. 7486 ◽  
Author(s):  
Oday Alsarraf ◽  
Jie Fan ◽  
Mohammad Dahrouj ◽  
C. James Chou ◽  
Phillip W. Yates ◽  
...  

2020 ◽  
pp. 019262332097637
Author(s):  
Anantharaman Muthuswamy ◽  
Henry Chen ◽  
Ying Hu ◽  
Oliver C. Turner ◽  
Olulanu H. Aina

Normal retina and its cell layers are essential for processing visual stimuli, and loss of its integrity has been documented in many disease processes. The numbers and the axonal processes of retinal ganglion cells are reduced substantially in glaucoma, leading to vision loss and blindness. Similarly, selective loss of photoreceptors in age-related macular degeneration and hereditary retinal dystrophies also results in the compromise of visual acuity. Development of genetically modified mice has led to increased understanding of the pathogenesis of many retinal diseases. Similarly, in this digital era, usage of modalities to quantify the retinal cell loss has grown exponentially leading to a better understanding of the suitability of animal models to study human retinal diseases. These quantification modalities provide valuable quantifiable data in studying pathogenesis and disease progression. This review will discuss the immunohistochemical markers for various retinal cells, available automated tools to quantify retinal cells, and present an example of retinal ganglion cell quantification using HALO image analysis platform. Additionally, we briefly review retinal cell types and subtypes, salient features of retina in various laboratory animal species, and a few of the main disease processes that affect retinal cell numbers in humans.


PLoS ONE ◽  
2020 ◽  
Vol 15 (3) ◽  
pp. e0229991
Author(s):  
Helle Østergaard Madsen ◽  
Shakoor Ba-Ali ◽  
Henrik Lund-Andersen ◽  
Klaus Martiny ◽  
Ida Hageman

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Masahito Yamagata ◽  
Wenjun Yan ◽  
Joshua R Sanes

Retinal structure and function have been studied in many vertebrate orders, but molecular characterization has been largely confined to mammals. We used single-cell RNA sequencing (scRNA-seq) to generate a cell atlas of the chick retina. We identified 136 cell types plus 14 positional or developmental intermediates distributed among the six classes conserved across vertebrates – photoreceptor, horizontal, bipolar, amacrine, retinal ganglion and glial cells. To assess morphology of molecularly defined types, we adapted a method for CRISPR-based integration of reporters into selectively expressed genes. For Müller glia, we found that transcriptionally distinct cells were regionally localized along the anterior-posterior, dorsal-ventral and central-peripheral retinal axes. We also identified immature photoreceptor, horizontal cell and oligodendrocyte types that persist into late embryonic stages. Finally, we analyzed relationships among chick, mouse and primate retinal cell classes and types. Our results provide a foundation for anatomical, physiological, evolutionary, and developmental studies of the avian visual system.


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