The change of microglia numbers within the mice retina, optic nerve and chiasm following intravitreal AAV2-GFP injection

2021 ◽  
pp. 112067212110490
Author(s):  
Yuanfei Ji ◽  
Bo Yu ◽  
Yikui Zhang ◽  
Wencan Wu
Keyword(s):  
Optic Nerve ◽  
Intravitreal Injection ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Optic Chiasm ◽  
Optimal Concentration ◽  
The Other ◽  
Retinal Ganglion ◽  
Sparse Labeling ◽  
Microglial Morphology

Purpose To explore the optimized concentration of AAV2-GFP for sparse transfection of retinal ganglion cells (RGCs) and optic nerve (ON), and to examine the changes of microglial morphology and distribution in the retina, optic nerve and chiasm after injection. Methods We defined the optimal concentration of AAV2-GFP for sparse labeling of RGCs and axons in WT mice. We further explored the changes of microglial morphology and distribution in the retina, optic nerve and chiasm after intravitreal injection in CX3CR1+/GFP mice. Results 14 days after intravitreal injection of AAV2-GFP, live imaging of the retina showed that fundus fluorescence was very strong and dense at 2.16 × 1011 VG/retina, 2.16 × 1010 VG/retina, 2.16 × 109 VG/retina. RGCs were sparsely marked at a concentration 1:1000 (2.16 × 108 VG/retina) and fundus fluorescence was weak. The transfected RGCs and axons were unevenly distributed in the retina and significantly more RGCs were transfected near the injection site of AAV2-GFP compared to the other sites of the flat-mounted retina. Microglia density increased significantly in the retina and part of optic nerve, but not in the optic chiasm. The morphology of microglia was largely unchanged. Conclusions AAV2-GFP was highly efficient and the optimal concentration of sparsely labeled RGCs was 1:1000 (2.16 × 108 VG/retina). After intravitreal injection of AAV2-GFP, the number of microglia increased partly. The morphology of microglia was comparable.

Melatonin As a Modulator of Degenerative and Regenerative Signaling Pathways in Injured Retinal Ganglion Cells

2019 ◽  
Vol 25 (28) ◽  
pp. 3057-3073 ◽  
Author(s):  
Kobra B. Juybari ◽  
Azam Hosseinzadeh ◽  
Habib Ghaznavi ◽  
Mahboobeh Kamali ◽  
Ahad Sedaghat ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Mitochondrial Dysfunction ◽  
Signaling Pathways ◽  
Retinal Ganglion Cells ◽  
Molecular Mechanisms ◽  
Nitrosative Stress ◽  
Ganglion Cells ◽  
Axon Growth ◽  
Nerve Fibers ◽  
Retinal Ganglion

Optic neuropathies refer to the dysfunction or degeneration of optic nerve fibers caused by any reasons including ischemia, inflammation, trauma, tumor, mitochondrial dysfunction, toxins, nutritional deficiency, inheritance, etc. Post-mitotic CNS neurons, including retinal ganglion cells (RGCs) intrinsically have a limited capacity for axon growth after either trauma or disease, leading to irreversible vision loss. In recent years, an increasing number of laboratory evidence has evaluated optic nerve injuries, focusing on molecular signaling pathways involved in RGC death. Trophic factor deprivation (TFD), inflammation, oxidative stress, mitochondrial dysfunction, glutamate-induced excitotoxicity, ischemia, hypoxia, etc. have been recognized as important molecular mechanisms leading to RGC apoptosis. Understanding these obstacles provides a better view to find out new strategies against retinal cell damage. Melatonin, as a wide-spectrum antioxidant and powerful freeradical scavenger, has the ability to protect RGCs or other cells against a variety of deleterious conditions such as oxidative/nitrosative stress, hypoxia/ischemia, inflammatory processes, and apoptosis. In this review, we primarily highlight the molecular regenerative and degenerative mechanisms involved in RGC survival/death and then summarize the possible protective effects of melatonin in the process of RGC death in some ocular diseases including optic neuropathies. Based on the information provided in this review, melatonin may act as a promising agent to reduce RGC death in various retinal pathologic conditions.

Specification of retinotectal connexions during development of the toad Xenopus laevis

Development ◽  
1980 ◽  
Vol 55 (1) ◽  
pp. 77-92
Author(s):  
S. C. Sharma ◽  
J. G. Hollyfield
Keyword(s):  
Xenopus Laevis ◽  
Ganglion Cell ◽  
Retinal Ganglion Cells ◽  
Optic Tectum ◽  
Ganglion Cells ◽  
The Other ◽  
Retinal Ganglion ◽  
Visual Projection ◽  
Series Of Experiments ◽  
The Right

The specification of central connexions of retinal ganglion cells was studied in Xenopus laevis. In one series of experiments, the right eye primordium was rotated 180° at embryonic stages 24–32. In the other series, the left eye was transplanted into the right orbit, and vice versa, with either 0° or 180° rotation. After metamorphosis the visual projections from the operated eye to the contralateral optic tectum were mapped electrophysiologically and compared with the normal retinotectal map. In all cases the visual projection map was rotated through the same angle as was indicated by the position of the choroidal fissure. The left eye exchanged into the right orbit retained its original axes and projected to the contralateral tectum. These results suggest that retinal ganglion cell connexions are specified before stage 24.

scholarly journals Photoreceptive retinal ganglion cells control the information rate of the optic nerve

2018 ◽  
Vol 115 (50) ◽  
pp. E11817-E11826 ◽  
Author(s):  
Nina Milosavljevic ◽  
Riccardo Storchi ◽  
Cyril G. Eleftheriou ◽  
Andrea Colins ◽  
Rasmus S. Petersen ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Retinal Ganglion Cells ◽  
Information Flow ◽  
Information Transfer ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Ambient Light ◽  
Visual Responses ◽  
Light Irradiance ◽  
The Brain

Information transfer in the brain relies upon energetically expensive spiking activity of neurons. Rates of information flow should therefore be carefully optimized, but mechanisms to control this parameter are poorly understood. We address this deficit in the visual system, where ambient light (irradiance) is predictive of the amount of information reaching the eye and ask whether a neural measure of irradiance can therefore be used to proactively control information flow along the optic nerve. We first show that firing rates for the retina’s output neurons [retinal ganglion cells (RGCs)] scale with irradiance and are positively correlated with rates of information and the gain of visual responses. Irradiance modulates firing in the absence of any other visual signal confirming that this is a genuine response to changing ambient light. Irradiance-driven changes in firing are observed across the population of RGCs (including in both ON and OFF units) but are disrupted in mice lacking melanopsin [the photopigment of irradiance-coding intrinsically photosensitive RGCs (ipRGCs)] and can be induced under steady light exposure by chemogenetic activation of ipRGCs. Artificially elevating firing by chemogenetic excitation of ipRGCs is sufficient to increase information flow by increasing the gain of visual responses, indicating that enhanced firing is a cause of increased information transfer at higher irradiance. Our results establish a retinal circuitry driving changes in RGC firing as an active response to alterations in ambient light to adjust the amount of visual information transmitted to the brain.

scholarly journals Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma

2007 ◽  
Vol 179 (7) ◽  
pp. 1523-1537 ◽  
Author(s):  
Gareth R. Howell ◽  
Richard T. Libby ◽  
Tatjana C. Jakobs ◽  
Richard S. Smith ◽  
F. Campbell Phalan ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Mouse Model ◽  
Retinal Ganglion Cells ◽  
Strong Evidence ◽  
Ganglion Cells ◽  
Lamina Cribrosa ◽  
Retinal Ganglion ◽  
Rich Region ◽  
Pattern Electroretinography ◽  
Axon Damage

Here, we use a mouse model (DBA/2J) to readdress the location of insult(s) to retinal ganglion cells (RGCs) in glaucoma. We localize an early sign of axon damage to an astrocyte-rich region of the optic nerve just posterior to the retina, analogous to the lamina cribrosa. In this region, a network of astrocytes associates intimately with RGC axons. Using BAX-deficient DBA/2J mice, which retain all of their RGCs, we provide experimental evidence for an insult within or very close to the lamina in the optic nerve. We show that proximal axon segments attached to their cell bodies survive to the proximity of the lamina. In contrast, axon segments in the lamina and behind the eye degenerate. Finally, the Wlds allele, which is known to protect against insults to axons, strongly protects against DBA/2J glaucoma and preserves RGC activity as measured by pattern electroretinography. These experiments provide strong evidence for a local insult to axons in the optic nerve.

scholarly journals Inverse oculomotor responses of achiasmatic mice expressing a transfer-defective Vax1 mutant

2020 ◽  
Author(s):  
Kwang Wook Min ◽  
Namsuk Kim ◽  
Jae Hoon Lee ◽  
Younghoon Sung ◽  
Museong Kim ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Optic Chiasm ◽  
Stereoscopic Vision ◽  
Retinal Ganglion ◽  
Visual Responses ◽  
Brain Areas ◽  
Optic Stalk ◽  
Intercellular Transfer ◽  
Oculomotor Responses

ABSTRACTIn animals that exhibit stereoscopic visual responses, the axons of retinal ganglion cells (RGCs) connect to brain areas bilaterally by forming a commissure called the optic chiasm (OC). Ventral anterior homeobox 1 (Vax1) contributes to formation of the OC, acting endogenously in optic pathway cells and exogenously in growing RGC axons. Here, we generated Vax1AA/AA mice expressing the Vax1AA mutant, which is selectively incapable of intercellular transfer. We found that RGC axons cannot take up Vax1AA protein from Vax1AA/AA mouse optic stalk (OS) cells, of which maturation is delayed, and fail to access the midline. Consequently, RGC axons of Vax1AA/AA mice connect exclusively to ipsilateral brain areas, resulting in the loss of stereoscopic vision and the inversed oculomotor responses. Together, our study provides physiological evidence for the necessity of intercellular transfer of Vax1 and the importance of the OC in binocular visual responses.

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