scholarly journals Glaucoma: A Degenerative Optic Neuropathy Related to Neuroinflammation?

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 535 ◽  
Author(s):  
Stéphane Mélik Parsadaniantz ◽  
Annabelle Réaux-le Goazigo ◽  
Anaïs Sapienza ◽  
Christophe Habas ◽  
Christophe Baudouin
Keyword(s):  
Optic Neuropathy ◽  
Ganglion Cells ◽  
Public Health Problem ◽  
Visual Pathways ◽  
Glaucomatous Optic Neuropathy ◽  
Major Public Health Problem ◽  
Retinal Ganglion ◽  
Current Therapies ◽  
Retinal Structure ◽  
Immunomodulatory Therapies

Glaucoma is one of the leading causes of irreversible blindness in the world and remains a major public health problem. To date, incomplete knowledge of this disease’s pathophysiology has resulted in current therapies (pharmaceutical or surgical) unfortunately having only a slowing effect on disease progression. Recent research suggests that glaucomatous optic neuropathy is a disease that shares common neuroinflammatory mechanisms with “classical” neurodegenerative pathologies. In addition to the death of retinal ganglion cells (RGCs), neuroinflammation appears to be a key element in the progression and spread of this disease. Indeed, early reactivity of glial cells has been observed in the retina, but also in the central visual pathways of glaucoma patients and in preclinical models of ocular hypertension. Moreover, neuronal lesions are not limited to retinal structure, but also occur in central visual pathways. This review summarizes and puts into perspective the experimental and clinical data obtained to date to highlight the need to develop neuroprotective and immunomodulatory therapies to prevent blindness in glaucoma patients.

scholarly journals Defocused Images Change Multineuronal Firing Patterns in the Mouse Retina

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 530 ◽  
Author(s):  
Seema Banerjee ◽  
Qin Wang ◽  
Chung Him So ◽  
Feng Pan
Keyword(s):  
Edge Detection ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Public Health Problem ◽  
Amacrine Cells ◽  
The United States ◽  
Mouse Retina ◽  
Major Public Health Problem ◽  
Retinal Ganglion ◽  
Firing Patterns

Myopia is a major public health problem, affecting one third of the population over 12 years old in the United States and more than 80% of people in Hong Kong. Myopia is attributable to elongation of the eyeball in response to defocused images that alter eye growth and refraction. It is known that the retina can sense the focus of an image, but the effects of defocused images on signaling of population of retinal ganglion cells (RGCs) that account either for emmetropization or refractive errors has still to be elucidated. Thorough knowledge of the underlying mechanisms could provide insight to understanding myopia. In this study, we found that focused and defocused images can change both excitatory and inhibitory conductance of ON alpha, OFF alpha and ON–OFF retinal ganglion cells in the mouse retina. The firing patterns of population of RGCs vary under the different powers of defocused images and can be affected by dopamine receptor agonists/antagonists’ application. OFF-delayed RGCs or displaced amacrine cells (dACs) with time latency of more than 0.3 s had synchrony firing with other RGCs and/or dACs. These spatial synchrony firing patterns between OFF-delayed cell and other RGCs/dACs were significantly changed by defocused image, which may relate to edge detection. The results suggested that defocused images induced changes in the multineuronal firing patterns and whole cell conductance in the mouse retina. The multineuronal firing patterns can be affected by dopamine receptors’ agonists and antagonists. Synchronous firing of OFF-delayed cells is possibly related to edge detection, and understanding of this process may reveal a potential therapeutic target for myopia patients.

scholarly journals Protective Effects of Oroxylin A on Retinal Ganglion Cells in Experimental Model of Anterior Ischemic Optic Neuropathy

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 902
Author(s):  
Jia-Ying Chien ◽  
Shu-Fang Lin ◽  
Yu-Yau Chou ◽  
Chi-Ying F. Huang ◽  
Shun-Ping Huang
Keyword(s):  
Retinal Ganglion Cells ◽  
Optic Neuropathy ◽  
Ganglion Cells ◽  
Ischemic Injury ◽  
Anterior Ischemic Optic Neuropathy ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Ischemic Optic Neuropathy ◽  
Retinal Ganglion ◽  
Oroxylin A

Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common cause of acute vision loss in older people, and there is no effective therapy. The effect of the systemic or local application of steroids for NAION patients remains controversial. Oroxylin A (OA) (5,7-dihydroxy-6-methoxyflavone) is a bioactive flavonoid extracted from Scutellariae baicalensis Georgi. with various beneficial effects, including anti-inflammatory and neuroprotective effects. A previous study showed that OA promotes retinal ganglion cell (RGC) survival after optic nerve (ON) crush injury. The purpose of this research was to further explore the potential actions of OA in ischemic injury in an experimental anterior ischemic optic neuropathy (rAION) rat model induced by photothrombosis. Our results show that OA efficiently attenuated ischemic injury in rats by reducing optic disc edema, the apoptotic death of retinal ganglion cells, and the infiltration of inflammatory cells. Moreover, OA significantly ameliorated the pathologic changes of demyelination, modulated microglial polarization, and preserved visual function after rAION induction. OA activated nuclear factor E2 related factor (Nrf2) signaling and its downstream antioxidant enzymes NAD(P)H:quinone oxidoreductase (NQO-1) and heme oxygenase 1 (HO-1) in the retina. We demonstrated that OA activates Nrf2 signaling, protecting retinal ganglion cells from ischemic injury, in the rAION model and could potentially be used as a therapeutic approach in ischemic optic neuropathy.

scholarly journals Retinal Neuropathy in IGT Stage of OLETF Rats: Another Characteristic Change of Diabetic Retinopathy

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Zhenhong Guo ◽  
Xiaoyue Sun ◽  
Juhong Yang ◽  
Jinlan Xie ◽  
Feifei Zhong ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Glucose Tolerance ◽  
Ganglion Cells ◽  
Normal Glucose Tolerance ◽  
Characteristic Change ◽  
Retinal Ganglion ◽  
Oletf Rats ◽  
Significant Damage ◽  
Normal Glucose ◽  
Retinal Structure

Aims. We investigated the changes of retinal structure in normal glucose tolerance (NGT), impaired glucose tolerance (IGT), diabetes mellitus (DM), and diabetic kidney disease (DKD) stages in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Methods. We assigned OLETF rats to four groups based on their OGTT results and 24 h urinary microalbumin (24 h UMA) levels: NGT, IGT, DM, and DKD groups. We observed the structural and the corresponding pathological changes and quantified the expression of HIF-1α, iNOS, NF-κB, VEGF, ICAM-1, and occludin in the retina. Results. Significant damage to the retinal structure, especially in retinal ganglion cells (RGCs), was observed in the IGT stage. The expression of HIF-1α, iNOS, NF-κB, VEGF, and ICAM-1 was significantly upregulated, while that of occludin was downregulated. Conclusion. Significant retinal neuropathy occurs in the IGT stage. Inflammation and hypoxia may damage the blood retina barrier (BRB), leading to diabetic retinopathy.

scholarly journals Oxidative Stress in Optic Neuropathies

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1538
Author(s):  
Berta Sanz-Morello ◽  
Hamid Ahmadi ◽  
Rupali Vohra ◽  
Sarkis Saruhanian ◽  
Kristine Karla Freude ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Optic Neuropathy ◽  
Vision Loss ◽  
Ganglion Cells ◽  
Redox System ◽  
Ischemic Optic Neuropathy ◽  
Retinal Ganglion ◽  
Oxidative Stress Biomarkers ◽  
Optic Disc Drusen ◽  
Advanced Stages

Increasing evidence indicates that changes in the redox system may contribute to the pathogenesis of multiple optic neuropathies. Optic neuropathies are characterized by the neurodegeneration of the inner-most retinal neurons, the retinal ganglion cells (RGCs), and their axons, which form the optic nerve. Often, optic neuropathies are asymptomatic until advanced stages, when visual impairment or blindness is unavoidable despite existing treatments. In this review, we describe systemic and, whenever possible, ocular redox dysregulations observed in patients with glaucoma, ischemic optic neuropathy, optic neuritis, hereditary optic neuropathies (i.e., Leber’s hereditary optic neuropathy and autosomal dominant optic atrophy), nutritional and toxic optic neuropathies, and optic disc drusen. We discuss aspects related to anti/oxidative stress biomarkers that need further investigation and features related to study design that should be optimized to generate more valuable and comparable results. Understanding the role of oxidative stress in optic neuropathies can serve to develop therapeutic strategies directed at the redox system to arrest the neurodegenerative processes in the retina and RGCs and ultimately prevent vision loss.

scholarly journals Electrophysiological markers of preclinical diagnosis of glaucomatous optic neuropathy

2021 ◽  
Vol 14 (1) ◽  
pp. 35-41
Author(s):  
M. O. Kirillova ◽  
M. V. Zueva ◽  
I. V. Tsapenko ◽  
A. N. Zhuravleva
Keyword(s):  
Optic Neuropathy ◽  
Ganglion Cells ◽  
Open Angle Glaucoma ◽  
Statistical Significance ◽  
Photopic Negative Response ◽  
Glaucomatous Optic Neuropathy ◽  
Functional Changes ◽  
Bright Flash ◽  
Pattern Size ◽  
Group 2

Purpose: to evaluate the changes in electrophysiological indicators reflecting various aspects of the function of retinal ganglion cells (RGC) and their axons in the early diagnosis of glaucomatous optic neuropathy (GON).Material and methods. Two clinical groups, (1) 35 patients (60 eyes) aged 49 to 70 with suspected glaucoma and (2) 16 patients (30 eyes) aged 43–68 with initial primary open-angle glaucoma (POAG), and a comparison group of 38 relatively healthy subjects (45 eyes) aged 42–70 were tested for pattern-reversed visual evoked potentials (PVEP), transient and stationary pattern-ERGs (PERG) according to ISCEV, and photopic negative response (PhNR).Results. The P100 amplitudes in both clinical groups differed significantly from the norm in PVEP on small and large patterns. The elongation of peak latency (T) of P100 compared with norm was significant for the stimulus 1° in group 2. In both groups of patients, increased variability of the temporal parameters of PERG and PVEP for small patterns was found. In groups 1 and 2, a decrease in the amplitude of P50 and N95 peaks of transient PERG for all stimuli was revealed, which was the most significant for the 0.3° pattern. In group 1, the N95 peak was significantly delayed in PERG for large patterns. A statistically significant reduction in the steady-state PERG's amplitude was found in the groups of suspected glaucoma and initial POAG. The sharpest changes were found for small (0.8° and 0.3°) patterns. The elongation of T compared to the norm was most pronounced for PERG at 0.3°, but due to the high variability of temporary indicators within the group, it had no statistical significance. The amplitude of PhNR was significantly different from the norm in the ERG for a flash of 3.0 cd·sec/m2.Conclusion. In patients with suspected glaucoma, a decrease in the P100 VEP amplitude with the simultaneous elongation of T may be considered as a criteria for the plastic stage at the level of lateral geniculate nucleus. Markers of functional changes in RGCs are the decrease in the amplitude of PhNR in response to bright flash, and P50 and N95 of PERG for pattern size 0.3°. The results indicate a greater vulnerability of the parvocellular system to early events in the development of GON.

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