scholarly journals The Retinal Ganglion Cell Transportome Identifies Proteins Transported to Axons and Presynaptic Compartments in the Visual System In Vivo

Cell Reports ◽  
2019 ◽  
Vol 28 (7) ◽  
pp. 1935-1947.e5
Author(s):  
Lucio M. Schiapparelli ◽  
Sahil H. Shah ◽  
Yuanhui Ma ◽  
Daniel B. McClatchy ◽  
Pranav Sharma ◽  
...  
Keyword(s):  
Visual System ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Retinal Ganglion

The metalloproteinase ADAM10 is required for retinal ganglion cell axon guidance in the developing visual systems

2007 ◽  
Vol 30 (4) ◽  
pp. 77
Author(s):  
Y. Y. Chen ◽  
C. L. Hehr ◽  
K. Atkinson-Leadbeater ◽  
J. C. Hocking ◽  
S. McFarlane
Keyword(s):  
Ganglion Cell ◽  
Axon Guidance ◽  
Retinal Ganglion Cell ◽  
Growth Cone ◽  
Expression Patterns ◽  
Optic Tract ◽  
Axon Growth ◽  
Proteolytic Processing ◽  
Retinal Ganglion

Background: The growth cone interprets cues in its environment in order to reach its target. We want to identify molecules that regulate growth cone behaviour in the developing embryo. We investigated the role of A disintegrin and metalloproteinase 10 (ADAM10) in axon guidance in the developing visual system of African frog, Xenopus laevis. Methods: We first examined the expression patterns of adam10 mRNA by in situ hybridization. We then exposed the developing optic tract to an ADAM10 inhibitor, GI254023X, in vivo. Lastly, we inhibited ADAM10 function in diencephalic neuroepithelial cells (through which retinal ganglion cell (RGC) axons extend) or RGCs by electroporating or transfecting an ADAM10 dominant negative (dn-adam10). Results: We show that adam10 mRNA is expressed in the dorsal neuroepithelium over the time RGC axons extend towards their target, the optic tectum. Second, pharmacological inhibition of ADAM10 in an in vivo exposed brain preparation causes the failure of RGC axons to recognize their target at low concentrations (0.5, 1 μM), and the failure of the axons to make a caudal turn in the mid-diencephalon at higher concentration (5 μM). Thus, ADAM10 function is required for RGC axon guidance at two key guidance decisions. Finally, molecular inhibition of ADAM10 function by electroporating dn-adam10 in the brain neuroepithelium causes defects in RGC axon target recognition (57%) and/or defects in caudal turn (12%), as seen with the pharmacological inhibitor. In contrast, molecular inhibition of ADAM10 within the RGC axons has no effect. Conclusions: These data argue strongly that ADAM10 acts cell non-autonomously within the neuroepithelium to regulate the guidance of RGC axons. This study shows for the first time that a metalloproteinase acts in a cell non-autonomous fashion to direct vertebrate axon growth. It will provide important insights into candidate molecules that could be used to reform nerve connections if destroyed because of injury or disease. References Hattori M, Osterfield M, Flanagan JG. Regulated cleavage of a contact-mediated axon repellent. Science 2000; 289(5483):1360-5. Janes PW, Saha N, Barton WA, Kolev MV, Wimmer-Kleikamp SH, Nievergall E, Blobel CP, Himanen JP, Lackmann M, Nikolov DB. Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans. Cell 2005; 123(2):291-304. Pan D, Rubin GM. Kuzbanian controls proteolytic processing of Notch and mediates lateral inhibition during Drosophila and vertebrate neurogenesis. Cell 1997; 90(2):271-80.

scholarly journals Exosome-Mediated Delivery of the Neuroprotective Peptide PACAP38 Promotes Retinal Ganglion Cell Survival and Axon Regeneration in Rats With Traumatic Optic Neuropathy

2021 ◽  
Vol 9 ◽  
Author(s):  
Tian Wang ◽  
Yiming Li ◽  
Miao Guo ◽  
Xue Dong ◽  
Mengyu Liao ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Optic Neuropathy ◽  
Axon Regeneration ◽  
Retinal Ganglion ◽  
Traumatic Optic Neuropathy ◽  
Fiber Layer

Traumatic optic neuropathy (TON) refers to optic nerve damage caused by trauma, leading to partial or complete loss of vision. The primary treatment options, such as hormonal therapy and surgery, have limited efficacy. Pituitary adenylate cyclase-activating polypeptide 38 (PACAP38), a functional endogenous neuroprotective peptide, has emerged as a promising therapeutic agent. In this study, we used rat retinal ganglion cell (RGC) exosomes as nanosized vesicles for the delivery of PACAP38 loaded via the exosomal anchor peptide CP05 (EXOPACAP38). EXOPACAP38 showed greater uptake efficiency in vitro and in vivo than PACAP38. The results showed that EXOPACAP38 significantly enhanced the RGC survival rate and retinal nerve fiber layer thickness in a rat TON model. Moreover, EXOPACAP38 significantly promoted axon regeneration and optic nerve function after injury. These findings indicate that EXOPACAP38 can be used as a treatment option and may have therapeutic implications for patients with TON.

All Brn3 genes can promote retinal ganglion cell differentiation in the chick

Development ◽  
2000 ◽  
Vol 127 (15) ◽  
pp. 3237-3247 ◽  
Author(s):  
W. Liu ◽  
S.L. Khare ◽  
X. Liang ◽  
M.A. Peters ◽  
X. Liu ◽  
...  
Keyword(s):  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Ganglion Cells ◽  
Cell Development ◽  
Large Set ◽  
Retinal Ganglion ◽  
Pou Domain ◽  
Temporal Expression Pattern ◽  
Cell Genesis

Targeted gene disruption studies in the mouse have demonstrated crucial roles for the Brn3 POU domain transcription factor genes, Brn3a, Brn3b, Brn3c (now called Pou4f1, Pou4f2, Pou4f3, respectively) in sensorineural development and survival. During mouse retinogenesis, the Brn3b gene is expressed in a large set of postmitotic ganglion cell precursors and is required for their early and terminal differentiation. In contrast, the Brn3a and Brn3c genes, which are expressed later in ganglion cells, appear to be dispensable for ganglion cell development. To understand the mechanism that causes the functional differences of Brn3 genes in retinal development, we employed a gain-of-function approach in the chick embryo. We find that Brn3b(l) and Brn3b(s), the two isoforms encoded by the Brn3b gene, as well as Brn3a and Brn3c all have similar DNA-binding and transactivating activities. We further find that the POU domain is minimally required for these activities. Consequently, we show that all these Brn3 proteins have a similar ability to promote development of ganglion cells when ectopically expressed in retinal progenitors. During chick retinogenesis, cBrn3c instead of cBrn3b exhibits a spatial and temporal expression pattern characteristic of ganglion cell genesis and its misexpression can also increase ganglion cell production. Based on these data, we propose that all Brn3 factors are capable of promoting retinal ganglion cell development, and that this potential may be limited by the order of expression in vivo.

In vivo imaging of retinal ganglion cell apoptosis

2013 ◽  
Vol 13 (1) ◽  
pp. 123-127 ◽  
Author(s):  
Joana Galvao ◽  
Benjamin M Davis ◽  
Maria Francesca Cordeiro
Keyword(s):  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Cell Apoptosis ◽  
In Vivo Imaging ◽  
Retinal Ganglion

scholarly journals Mitochondrial pathogenic mechanism and degradation in optineurin E50K mutation-mediated retinal ganglion cell degeneration

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Myoung Sup Shim ◽  
Yuji Takihara ◽  
Keun-Young Kim ◽  
Takeshi Iwata ◽  
Beatrice Y. J. T. Yue ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Open Angle Glaucoma ◽  
Mitochondrial Fission ◽  
Retinal Ganglion ◽  
Cell Degeneration ◽  
Transport Dynamics

Abstract Mutations in optineurin (OPTN) are linked to the pathology of primary open angle glaucoma (POAG) and amyotrophic lateral sclerosis. Emerging evidence indicates that OPTN mutation is involved in accumulation of damaged mitochondria and defective mitophagy. Nevertheless, the role played by an OPTN E50K mutation in the pathogenic mitochondrial mechanism that underlies retinal ganglion cell (RGC) degeneration in POAG remains unknown. We show here that E50K expression induces mitochondrial fission-mediated mitochondrial degradation and mitophagy in the axons of the glial lamina of aged E50K−tg mice in vivo. While E50K activates the Bax pathway and oxidative stress, and triggers dynamics alteration-mediated mitochondrial degradation and mitophagy in RGC somas in vitro, it does not affect transport dynamics and fission of mitochondria in RGC axons in vitro. These results strongly suggest that E50K is associated with mitochondrial dysfunction in RGC degeneration in synergy with environmental factors such as aging and/or oxidative stress.

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