In vivo effects of single or combined topical neuroprotective and regenerative agents on degeneration of retinal ganglion cells in rat optic nerve crush model

Kitamura, Yuta; Bikbova, Guzel; Baba, Takayuki; Yamamoto, Shuichi; Oshitari, Toshiyuki

doi:10.1038/s41598-018-36473-2

Cited by 28 publications

(26 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The above-mentioned preventative effects of Citicoline (administered by eye drops) were hypothesized on the basis of reduced neuroretinal structural abnormalities. [84] Similarly, in the optic nerve crush model, with respect to PBS-treated eyes, rats treated with Citicoline combined with tauroursodeoxycholic acid and neurotrophin-4 showed a higher density of RCGs and higher number of RGCs axons [85].…”

Section: Discussionmentioning

confidence: 99%

Neuroenhancement and neuroprotection by oral solution citicoline in non-arteritic ischemic optic neuropathy as a model of neurodegeneration: A randomized pilot study

et al. 2019

View full text Add to dashboard Cite

Purpose To evaluate whether treatment with Citicoline in oral solution (OS-Citicoline) would increase visual function, retinal ganglion cells (RGCs) function, and neural conduction along visual pathways (neuroenhancement), and/or induce preservation of RGCs fibers’ loss (neuroprotection) in non-arteritic ischemic optic neuropathy (NAION), a human model of neurodegeneration. Methods Thirty-six patients with NAION and 20 age-matched controls were enrolled. Nineteen NAION patients received 500 mg/day of OS-Citicoline for a 6-month period followed by 3-month of wash-out (NC Group); 17 NAION patients were not treated (NN Group) from baseline to 9 months. In all subjects at baseline, and in NC and NN eyes at 6 and 9 months of follow-up, we assessed Visual Acuity (VA), Pattern Electroretinogram (PERG), Visual Evoked Potentials (VEP), retinal nerve fiber layer thickness (RNFL-T), and Humphrey 24–2 visual field mean deviation (HFA MD). Mean differences were statistically evaluated with ANOVA between Groups, and linear correlations were analysed with Pearson’s test. Results At 6 months, significant differences between groups for all parameters were observed (ANOVA, p<0.01). In NC eyes, VA increased, PERG responses increased, VEP recordings improved and were significantly correlated with increases in HFA MD (p<0.01), and RNFL-T was unmodified or improved. In contrast, in NN eyes, VA, PERG, VEP responses, RNFL-T, and HFA MD were further worsened. Significant differences were still present at 9-month follow-up in the NN Group and after 3 months of OS-Citicoline wash-out in NC eyes. Conclusions OS-Citicoline treatment induced neuroenhancement (improvement in RGCs function and neural conduction along visual pathways related to improvement of visual field defects) and neuroprotection (unmodified or improved RNFL morphological condition) in a human model of NAION involving fast RGCs degeneration. Trial registration ClinicalTrials.gov NCT03758118 .

show abstract

Section: Discussionmentioning

confidence: 99%

Neuroenhancement and neuroprotection by oral solution citicoline in non-arteritic ischemic optic neuropathy as a model of neurodegeneration: A randomized pilot study

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Likewise, dual injection of neural stem cells releasing GDNF or CNTF showed a synergistic effect after ONI [134]. A very recent study of Kitamura et al [135] compared the in vivo effects of single and combined NTF administration on RGC survival in adult rats after ONI. Once more, they showed that the combinatorial approach was the most effective one.…”

Section: Ntfs As Neuroprotective Therapy In Glaucoma: What Informamentioning

confidence: 99%

“…Once more, they showed that the combinatorial approach was the most effective one. Of note, besides NT-4, they studied rather unconventional NTFs: tauroursodeoxycholic acid and citicoline [135]. In sharp contrast, using a laser-induced glaucoma model, Pease et al [136] were unable to show an additive effect of dual injection of viral vectors overexpressing BDNF or CNTF on RGC survival.…”

Section: Ntfs As Neuroprotective Therapy In Glaucoma: What Informamentioning

confidence: 99%

See 1 more Smart Citation

Target-Derived Neurotrophic Factor Deprivation Puts Retinal Ganglion Cells on Death Row: Cold Hard Evidence and Caveats

Claes

Groef

Moons

2019

IJMS

View full text Add to dashboard Cite

Glaucoma and other optic neuropathies are characterized by axonal transport deficits. Axonal cargo travels back and forth between the soma and the axon terminus, a mechanism ensuring homeostasis and the viability of a neuron. An example of vital molecules in the axonal cargo are neurotrophic factors (NTFs). Hindered retrograde transport can cause a scarcity of those factors in the retina, which in turn can tilt the fate of retinal ganglion cells (RGCs) towards apoptosis. This postulation is one of the most widely recognized theories to explain RGC death in the disease progression of glaucoma and is known as the NTF deprivation theory. For several decades, research has been focused on the use of NTFs as a novel neuroprotective glaucoma treatment. Until now, results in animal models have been promising, but translation to the clinic has been highly disappointing. Are we lacking important knowledge to lever NTF therapies towards the therapeutic armamentarium? Or did we get the wrong end of the stick regarding the NTF deprivation theory? In this review, we will tackle the existing evidence and caveats advocating for and against the target-derived NTF deprivation theory in glaucoma, whilst digging into associated therapy efforts.

show abstract

“…TUDCA treatment ameliorates photoreceptor death in naturally occurring, knockout, and transgenic rodent models of retinal diseases [ 3 , 7 , 8 , 9 , 10 , 11 ]. TUDCA also shows the protection of ganglion cells from n -methyl- d -aspartate-induced retinal damage in rats [ 12 ] and a rat model involving crushed optic nerve [ 13 ]. Recently, we have examined the protective effect of TUDCA against photoreceptor degeneration in a retinitis pigmentosa GTPase regulator ( Rpgr ) knockout mouse model of retinitis pigmentosa.…”

Section: Introductionmentioning

confidence: 99%

Tauroursodeoxycholic Acid Protects Retinal Pigment Epithelial Cells from Oxidative Injury and Endoplasmic Reticulum Stress In Vitro

et al. 2020

View full text Add to dashboard Cite

Retinal degeneration is characterized by the dysfunction of retinal cells. Oxidative and endoplasmic reticulum (ER) stress play an important role in the pathogenesis and progression of retinal degeneration. Tauroursodeoxycholic acid (TUDCA) has been demonstrated to have protective effects in in vitro and in vivo retinal degeneration models. To fully understand the molecular mechanisms of TUDCA’s protection, we first treated human retinal pigment epithelial (RPE) cells, ARPE-19, with H2O2 or H2O2 plus TUDCA for 24 h. RPE cells co-exposed to TUDCA had higher cell viability and lower cell death rate compared to cells exposed to H2O2 alone. TUDCA significantly increased antioxidant capacity in H2O2-treated RPE cells by decreasing the generation of reactive oxygen species (ROS) and Malondialdehyde (MDA), upregulating the expression of antioxidant genes, and increasing the generation of glutathione (GSH). TUDCA also inhibited inflammation in H2O2-challenged RPE cells by decreasing the expression of proinflammatory cytokines. Furthermore, TUDCA suppressed thapsigargin-induced ER stress in RPE cells, as demonstrated by decreased the expression of CCAAT-enhancer-binding protein homologous protein (CHOP) and apoptosis. Our present study suggests that TUDCA can protect RPE cells against oxidative damage, inflammation, and ER stress and may benefit patients with retinal degeneration.

show abstract

In vivo effects of single or combined topical neuroprotective and regenerative agents on degeneration of retinal ganglion cells in rat optic nerve crush model

Cited by 28 publications

References 35 publications

Neuroenhancement and neuroprotection by oral solution citicoline in non-arteritic ischemic optic neuropathy as a model of neurodegeneration: A randomized pilot study

Neuroenhancement and neuroprotection by oral solution citicoline in non-arteritic ischemic optic neuropathy as a model of neurodegeneration: A randomized pilot study

Target-Derived Neurotrophic Factor Deprivation Puts Retinal Ganglion Cells on Death Row: Cold Hard Evidence and Caveats

Tauroursodeoxycholic Acid Protects Retinal Pigment Epithelial Cells from Oxidative Injury and Endoplasmic Reticulum Stress In Vitro

Contact Info

Product

Resources

About