scholarly journals Polydopamine nanoparticles attenuate retina ganglion cell degeneration and restore visual function after optic nerve injury

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiaotong Lou ◽  
Yuanyuan Hu ◽  
Hong Zhang ◽  
Jia Liu ◽  
Yin Zhao
Keyword(s):  
Optic Nerve ◽  
Visual Function ◽  
Ganglion Cells ◽  
Drug Carrier ◽  
Neurovascular Unit ◽  
Cell Degeneration ◽  
Nerve Crush ◽  
Vein Occlusion ◽  
Expression Of Genes ◽  
Retina Ganglion Cell

Abstract Background Oxidative stress contributes to retina ganglion cells (RGCs) loss in variety of ocular diseases, including ocular trauma, ocular vein occlusion, and glaucoma. Scavenging the excessed reactive oxygen species (ROS) in retinal neurovascular unit could be beneficial to RGCs survival. In this study, a polydopamine (PDA)-based nanoplatform is developed to protect RGCs. Results The PDA nanoparticles efficiently eliminate multi-types of ROS, protect endothelia and neuronal cells from oxidative damage, and inhibit microglia activation in retinas. In an optic nerve crush (ONC) model, single intravitreal injection of PDA nanoparticles could significantly attenuate RGCs loss via eliminating ROS in retinas, reducing the inflammatory response and maintaining barrier function of retinal vascular endothelia. Comparative transcriptome analysis of the retina implied that PDA nanoparticles improve RGCs survival probably by altering the expression of genes involved in inflammation and ROS production. Importantly, as a versatile drug carrier, PDA nanoparticles could deliver brimonidine (a neuroprotection drug) to synergistically attenuate RGCs loss and promote axon regeneration, thus restore visual function. Conclusions The PDA nanoparticle-based therapeutic nanoplatform displayed excellent performance in ROS elimination, providing a promising probability for treating retinal degeneration diseases. Graphical Abstract

scholarly journals Polydopamine Nanoparticles Attenuate Retina Ganglion Cell Degeneration and Restore Visual Function After Optic Nerve Injury

2021 ◽  
Author(s):  
Xiaotong Lou ◽  
Yuanyuan Hu ◽  
Hong Zhang ◽  
Jia Liu ◽  
Yin Zhao
Keyword(s):  
Optic Nerve ◽  
Visual Function ◽  
Ganglion Cells ◽  
Drug Carrier ◽  
Neurovascular Unit ◽  
Cell Degeneration ◽  
Nerve Crush ◽  
Vein Occlusion ◽  
Expression Of Genes ◽  
Retina Ganglion Cell

Abstract Background: Oxidative stress contributes to retina ganglion cells (RGCs) loss in variety of ocular diseases, including ocular trauma, ocular vein occlusion, and glaucoma. Scavenging the excessed reactive oxygen species (ROS) in retinal neurovascular unit could be beneficial to RGCs survival. In this study, a polydopamine (PDA)-based nanoplatform is developed to protect RGCs. Results: The PDA nanoparticles efficiently eliminate multi-types of ROS, protect endothelia and neuronal cells from oxidative damage, and inhibit microglia activation in retinas. In an optic nerve crush (ONC) model, single intravitreal injection of PDA nanoparticles could significantly attenuate RGCs loss via eliminating ROS in retinas, reducing the inflammatory response and maintaining barrier function of retinal vascular endothelia. Comparative transcriptome analysis of the retina implied that PDA nanoparticles improve RGCs survival probably by altering the expression of genes involved in inflammation and ROS production. Importantly, as a versatile drug carrier, PDA nanoparticles could deliver brimonidine (a neuroprotection drug) to synergistically attenuate RGCs loss and promote axon regeneration, thus restore visual function. Conclusions: the PDA nanoparticle-based therapeutic nanoplatform displayed excellent performance in ROS elimination, providing a promising probability for treating retinal degeneration diseases.

scholarly journals Optic nerve astrocyte reactivity protects function in experimental glaucoma and other nerve injuries

2017 ◽  
Vol 214 (5) ◽  
pp. 1411-1430 ◽  
Author(s):  
Daniel Sun ◽  
Sara Moore ◽  
Tatjana C. Jakobs
Keyword(s):  
Optic Nerve ◽  
Visual Function ◽  
Ganglion Cells ◽  
Protective Role ◽  
Nerve Injuries ◽  
Nerve Crush ◽  
Knock Out ◽  
Experimental Glaucoma ◽  
Stat3 Signaling ◽  
Optic Nerve Injuries

Reactive remodeling of optic nerve head astrocytes is consistently observed in glaucoma and other optic nerve injuries. However, it is unknown whether this reactivity is beneficial or harmful for visual function. In this study, we used the Cre recombinase (Cre)–loxP system under regulation of the mouse glial fibrillary acidic protein promoter to knock out the transcription factor signal transducer and activator of transcription 3 (STAT3) from astrocytes and test the effect this has on reactive remodeling, ganglion cell survival, and visual function after experimental glaucoma and nerve crush. After injury, STAT3 knockout mice displayed attenuated astrocyte hypertrophy and reactive remodeling; astrocytes largely maintained their honeycomb organization and glial tubes. These changes were associated with increased loss of ganglion cells and visual function over a 30-day period. Thus, reactive astrocytes play a protective role, preserving visual function. STAT3 signaling is an important mediator of various aspects of the reactive phenotype within optic nerve astrocytes.

scholarly journals Rescue of retinal ganglion cells in optic nerve injury using cell-selective AAV mediated delivery of SIRT1

Gene Therapy ◽  
2021 ◽  
Author(s):  
Ahmara G. Ross ◽  
Devin S. McDougald ◽  
Reas S. Khan ◽  
Thu T. Duong ◽  
Kimberly E. Dine ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Ganglion Cell ◽  
Optic Neuropathy ◽  
Visual Function ◽  
Ganglion Cells ◽  
Transduction Efficiency ◽  
Retinal Ganglion ◽  
Optokinetic Response ◽  
Nerve Crush

AbstractSIRT1 prevents retinal ganglion cell (RGC) loss in models of optic neuropathy following pharmacologic activation or genetic overexpression. The exact mechanism of loss is not known, prior evidence suggests this is through oxidative stress to either neighboring cells or RGC specifically. We investigated the neuroprotective potential of RGC-selective SIRT1 gene therapy in the optic nerve crush (ONC) model. We hypothesized that AAV-mediated overexpression of SIRT1 in RGCs reduces RGC loss, thereby preserving visual function. Cohorts of C57Bl/6J mice received intravitreal injection of experimental or control AAVs using either a ganglion cell promoter or a constitutive promoter and ONC was performed. Visual function was examined by optokinetic response (OKR) for 7 days following ONC. Retina and optic nerves were harvested to investigate RGC survival by immunolabeling. The AAV7m8-SNCG.SIRT1 vector showed 44% transduction efficiency for RGCs compared with 25% (P > 0.05) by AAV2-CAG.SIRT1, and AAV7m8-SNCG.SIRT1 drives expression selectively in RGCs in vivo. Animals modeling ONC demonstrated reduced visual acuity compared to controls. Intravitreal delivery of AAV7m8-SNCG.SIRT1 mediated significant preservation of the OKR and RGC survival compared to AAV7m8-SNCG.eGFP controls, an effect not seen with the AAV2 vector. RGC-selective expression of SIRT1 offers a targeted therapy for an animal model with significant ganglion cell loss. Over-expression of SIRT1 through AAV-mediated gene transduction suggests a RGC selective component of neuro-protection using the ONC model. This study expands our understanding of SIRT1 mediated neuroprotection in the context of compressive or traumatic optic neuropathy, making it a strong therapeutic candidate for testing in all optic neuropathies.

Inherited glaucoma in DBA/2J mice: Pertinent disease features for studying the neurodegeneration

2005 ◽  
Vol 22 (5) ◽  
pp. 637-648 ◽  
Author(s):  
RICHARD T. LIBBY ◽  
MICHAEL G. ANDERSON ◽  
IOK-HOU PANG ◽  
ZACHARY H. ROBINSON ◽  
OLGA V. SAVINOVA ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Ganglion Cells ◽  
The Elderly ◽  
Nerve Degeneration ◽  
Retinal Ganglion ◽  
Cell Degeneration ◽  
Future Studies ◽  
Age Related ◽  
Iop Elevation ◽  
Mechanistic Basis

The glaucomas are neurodegenerative diseases involving death of retinal ganglion cells and optic nerve head excavation. A major risk factor for this neurodegeneration is a harmfully elevated intraocular pressure (IOP). Human glaucomas are typically complex, progressive diseases that are prevalent in the elderly. Family history and genetic factors are clearly important in human glaucoma. Mouse studies have proven helpful for investigating the genetic and mechanistic basis of complex diseases. We previously reported inherited, age-related progressive glaucoma in DBA/2J mice. Here, we report our updated findings from studying the disease in a large number of DBA/2J mice. The period when mice have elevated IOP extends from 6 months to 16 months, with 8–9 months representing an important transition to high IOP for many mice. Optic nerve degeneration follows IOP elevation, with the majority of optic nerves being severely damaged by 12 months of age. This information should help with the design of experiments, and we present the data in a manner that will be useful for future studies of retinal ganglion cell degeneration and optic neuropathy.

Axon Regeneration in the Mammalian Optic Nerve

2020 ◽  
Vol 6 (1) ◽  
pp. 195-213
Author(s):  
Philip R. Williams ◽  
Larry I. Benowitz ◽  
Jeffrey L. Goldberg ◽  
Zhigang He
Keyword(s):  
Optic Nerve ◽  
Ganglion Cells ◽  
Traumatic Injury ◽  
Optic Glioma ◽  
Retinal Ganglion ◽  
Degenerative Diseases ◽  
Nerve Crush ◽  
Neural Repair ◽  
Molecular Logic ◽  
Injury Models

The damage or loss of retinal ganglion cells (RGCs) and their axons accounts for the visual functional defects observed after traumatic injury, in degenerative diseases such as glaucoma, or in compressive optic neuropathies such as from optic glioma. By using optic nerve crush injury models, recent studies have revealed the cellular and molecular logic behind the regenerative failure of injured RGC axons in adult mammals and suggested several strategies with translational potential. This review summarizes these findings and discusses challenges for developing clinically applicable neural repair strategies.

A second episode of ganglion cell death takes place when an optic nerve regenerates for a second time in the frog

1993 ◽  
Vol 10 (2) ◽  
pp. 297-301 ◽  
Author(s):  
L. D. Beazley ◽  
J.E. Darby
Keyword(s):  
Cell Death ◽  
Optic Nerve ◽  
Ganglion Cell ◽  
Ganglion Cells ◽  
Cresyl Violet ◽  
Retinal Ganglion ◽  
Nerve Crush ◽  
Optic Nerve Regeneration ◽  
Ability To Regenerate ◽  
Ganglion Cell Death

AbstractWe have previously reported that during optic nerve regeneration in the frog, 30–40% of retinal ganglion cells die, the loss being complete within 10 weeks. In the present study, we crushed the optic nerve, waited 10 weeks, and then recrushed the nerve at the same site. Retinae were examined 10 weeks later. We estimated ganglion cell numbers from cresyl-violet-stained wholemounts and found a fall of 53% compared to normals. The loss was significantly greater than the losses of 36% and 35%, respectively, in frogs which received a single optic nerve crush and were examined 10 or 20–24 weeks later. The results indicate that a second episode of ganglion cell death took place when the optic nerve regenerated a second time. We conclude that ganglion cells in the frog are not comprised of two subpopulations, only one of which intrinsically possesses the ability to regenerate.

Valproate promotes survival of retinal ganglion cells in a rat model of optic nerve crush

Neuroscience ◽  
2012 ◽  
Vol 224 ◽  
pp. 282-293 ◽  
Author(s):  
Z.Z. Zhang ◽  
Y.Y. Gong ◽  
Y.H. Shi ◽  
W. Zhang ◽  
X.H. Qin ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Retinal Ganglion Cells ◽  
Rat Model ◽  
Ganglion Cells ◽  
Optic Nerve Crush ◽  
Retinal Ganglion ◽  
Nerve Crush
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