scholarly journals Human Umbilical Cord-Mesenchymal Stem Cells Survive and Migrate within the Vitreous Cavity and Ameliorate Retinal Damage in a Novel Rat Model of Chronic Glaucoma

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yao Wang ◽  
Jiexuan Lv ◽  
Changquan Huang ◽  
Xiaohong Li ◽  
Yongxiong Chen ◽  
...  
Keyword(s):  
Umbilical Cord ◽  
Rat Model ◽  
Fluorescent Protein ◽  
Ganglion Cells ◽  
Therapeutic Option ◽  
Vitreous Cavity ◽  
Human Umbilical Cord ◽  
Retinal Damage ◽  
Neuroprotective Effects ◽  
Chronic Glaucoma

Glaucoma is the leading cause of irreversible blindness worldwide, and pathologically elevated intraocular pressure (IOP) is the major risk factor. Neuroprotection is one of the potential therapies for glaucomatous retinal damage. Intravitreal mesenchymal stem cell (MSC) transplantation provides a viable therapeutic option, and human umbilical cord- (hUC-) MSCs are attractive candidates for cell-based neuroprotection. Here, we investigated the ability of transplanted hUC-MSCs to survive and migrate within the vitreous cavity and their neuroprotective effects on chronic glaucomatous retina. For this, we developed a chronic ocular hypertension (COH) rat model through the intracameral injection of allogeneic Tenon’s fibroblasts. Green fluorescent protein-transduced hUC-MSCs were then injected into the vitreous cavity one week after COH induction. Results showed that a moderate IOP elevation lasted for two months. Transplanted hUC-MSCs migrated toward the area of damaged retina, but did not penetrate into the retina. The hUC-MSCs survived for at least eight weeks in the vitreous cavity. Moreover, the hUC-MSCs were efficient at decreasing the loss of retinal ganglion cells; retinal damage was attenuated through the inhibition of apoptosis. In this study, we have developed a novel COH rat model and demonstrated the prolonged neuroprotective potential of intravitreal hUC-MSCs in chronic glaucoma.

scholarly journals Exosomes Derived from TIMP2-Modified Human Umbilical Cord Mesenchymal Stem Cells Enhance the Repair Effect in Rat Model with Myocardial Infarction Possibly by the Akt/Sfrp2 Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-19 ◽  
Author(s):  
Jing Ni ◽  
Xijun Liu ◽  
Yiheng Yin ◽  
Peiyu Zhang ◽  
Ya-Wei Xu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cardiac Function ◽  
Umbilical Cord ◽  
Rat Model ◽  
Therapeutic Option ◽  
Human Umbilical Cord ◽  
Therapeutic Effects ◽  
Ecm Remodeling

Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) are a promising new therapeutic option for myocardial infarction (MI). The tissue matrix metalloproteinase inhibitor 2, also known as TIMP2, is a member of the tissue inhibitor family of metalloproteinases. Since TIMP2-mediated inhibition of matrix metalloproteinases (MMPs) is a key determinant of post-MI remodeling, we analyzed the therapeutic effects of exosomes derived from TIMP2-overexpressing hucMSCs (huc-exoTIMP2) on the MI rat model. The huc-exoTIMP2 significantly improved in vivo cardiac function as measured by echocardiography and promoted angiogenesis in MI injury. It also restricted extracellular matrix (ECM) remodeling, as indicated by the reduced collagen deposition. In addition, huc-exoTIMP2 administration increased the in situ expression of the antiapoptotic Bcl-2 and decreased that of the proapoptotic Bax and pro-caspase-9 in the infracted myocardium. Meanwhile, huc-exoTIMP2 upregulated superoxide dismutase (SOD) as well as glutathione (GSH) and decreased the malondialdehyde (MDA) level in MI models. In vitro huc-exoTIMP2 pretreatment could inhibit H2O2-mediated H9C2-cardiomyocyte apoptosis and promote human umbilical vein endothelial cell (HUVEC) proliferation, migration, and tube formation, as well as decrease TGFβ-induced MMP2, MMP9, and α-SMA secretion by cardiac fibroblasts (CFs). Besides that, huc-exoTIMP2 pretreatment also increased the expression of Akt phosphorylation in the infarcted myocardium, which may relate to a high level of secreted frizzled-related protein 2 (Sfrp2) in huc-exoTIMP2, indicating a mechanistic basis of its action. Importantly, Sfrp2 knockdown in huc-exoTIMP2 abrogated the protective effects. Taken together, huc-exoTIMP2 improved cardiac function by alleviating MI-induced oxidative stress and ECM remodeling, partly via the Akt/Sfrp2 pathway.

scholarly journals hUC-MSCs Exert a Neuroprotective Effect via Anti-apoptotic Mechanisms in a Neonatal HIE Rat Model

2019 ◽  
Vol 28 (12) ◽  
pp. 1552-1559 ◽  
Author(s):  
Jianwei Xu ◽  
Zhanhui Feng ◽  
Xianyao Wang ◽  
Ying Xiong ◽  
Lan Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Rat Model ◽  
Caspase 3 ◽  
Neuroprotective Effect ◽  
Hypoxic Ischemic Encephalopathy ◽  
Human Umbilical Cord ◽  
Motor Functions ◽  
Ischemic Encephalopathy

In this study, we investigated how human umbilical cord mesenchymal stem cells exerted a neuroprotective effect via antiapoptotic mechanisms in a neonatal hypoxic-ischemic encephalopathy rat model. A total of 78 10-day old (P10) rats were used. After human umbilical cord mesenchymal stem cells were collected from human umbilical cords and amplified in culture, they were administered to rat subjects 1 h after induced hypoxic-ischemic encephalopathy treatment. The short-term (48 h) and long-term (28 day) outcomes were evaluated after human umbilical cord mesenchymal stem cells treatment using neurobehavioral function assessment. Triphenyltetrazolium chloride monohydrate staining was performed at 48 h. Beclin-2 and caspase-3 levels were evaluated with Western blot and real time polymerase chain reaction at 48 h. Human umbilical cord mesenchymal stem cells were collected and administrated to hypoxic-ischemic encephalopathy pups by intracerebroventricular injection. Hypoxic-ischemic encephalopathy typically induced significant delay in development and caused impairment in both cognitive and motor functions in rat subjects. Human umbilical cord mesenchymal stem cells were shown to ameliorate hypoxic-ischemic encephalopathy-induced damage and improve both cognitive and motor functions. Although hypoxic-ischemic encephalopathy induced significant expression of caspase-3 and Beclin-2, human umbilical cord mesenchymal stem cells decreased the expression of both of them. Human umbilical cord mesenchymal stem cells may serve as a potential treatment to ameliorate brain injury in hypoxic-ischemic encephalopathy patients.

The anemia of the newborn induces erythropoietin expression in the developing mouse retina

2010 ◽  
Vol 299 (1) ◽  
pp. R111-R118 ◽  
Author(s):  
N. Scheerer ◽  
N. Dünker ◽  
S. Imagawa ◽  
M. Yamamoto ◽  
N. Suzuki ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Fluorescent Protein ◽  
Ganglion Cells ◽  
Retinal Development ◽  
Transforming Growth Factor Β ◽  
Neuroprotective Activity ◽  
Mouse Retina ◽  
Mrna Levels ◽  
Neuroprotective Effects

The hematopoietic hormone erythropoietin (Epo), regularly produced by the kidneys and the liver, is also expressed in neuronal tissue, where it has been found to mediate paracrine neuroprotective effects. In most studies exploring the rescue effects of Epo, apoptosis was exogenously induced by different cell death stimuli. Herein, we set out to study the expression and function of Epo in physiologically occurring apoptosis in a model of retinal development. We made use of an organotypic retinal wholemount culture system that resembles the physiological in vivo situation with cell connections still retained. Epo mRNA expression in the retina, liver, and kidney showed a significant increase during early development, coinciding with the anemia of the newborn. In the retina of Epo-green fluorescent protein transgenic mice, Epo-expressing cells were identified and found to be distributed in the retinal ganglion cell layer. Treatment of retinal wholemount cultures with recombinant Epo resulted in a significant decrease of apoptotic ganglion cells as well as photoreceptor cells throughout retinal development. Moreover, transforming growth factor-β-induced apoptosis was completely antagonized by Epo when both factors were simultaneously applied. Investigations on the signaling pathway revealed a decrease in Bax mRNA levels in Epo-treated retinal cells. We conclude that Epo exerts wide and prolonged neuroprotective activity in physiologically occurring apoptosis and thus contributes to proper retinal development.

scholarly journals A Topical Formulation of Melatoninergic Compounds Exerts Strong Hypotensive and Neuroprotective Effects in a Rat Model of Hypertensive Glaucoma

2020 ◽  
Vol 21 (23) ◽  
pp. 9267
Author(s):  
Massimo Dal Monte ◽  
Maurizio Cammalleri ◽  
Rosario Amato ◽  
Salvatore Pezzino ◽  
Roberta Corsaro ◽  
...  
Keyword(s):  
Rat Model ◽  
Ganglion Cells ◽  
Hypotensive Activity ◽  
Retinal Ganglion ◽  
Topical Formulation ◽  
Adrenergic Agonist ◽  
Neuroprotective Effects ◽  
Neuroprotective Efficacy ◽  
Iop Elevation ◽  
Ocular Health

Melatonin is of great importance for regulating several eye processes, including pressure homeostasis. Melatonin in combination with agomelatine has been recently reported to reduce intraocular pressure (IOP) with higher efficacy than each compound alone. Here, we used the methylcellulose (MCE) rat model of hypertensive glaucoma, an optic neuropathy characterized by the apoptotic death of retinal ganglion cells (RGCs), to evaluate the hypotensive and neuroprotective efficacy of an eye drop nanomicellar formulation containing melatonin/agomelatine. Eye tissue distribution of melatonin/agomelatine in healthy rats was evaluated by HPLC/MS/MS. In the MCE model, we assessed by tonometry the hypotensive efficacy of melatonin/agomelatine. Neuroprotection was revealed by electroretinography; by levels of inflammatory and apoptotic markers; and by RGC density. The effects of melatonin/agomelatine were compared with those of timolol (a beta blocker with prevalent hypotensive activity) or brimonidine (an alpha 2 adrenergic agonist with potential neuroprotective efficacy), two drugs commonly used to treat glaucoma. Both melatonin and agomelatine penetrate the posterior segment of the eye. In the MCE model, IOP elevation was drastically reduced by melatonin/agomelatine with higher efficacy than that of timolol or brimonidine. Concomitantly, gliosis-related inflammation and the Bax-associated apoptosis were partially prevented, thus leading to RGC survival and recovered retinal dysfunction. We suggest that topical melatoninergic compounds might be beneficial for ocular health.

scholarly journals Brazilian Green Propolis Protects against Retinal Damage In Vitro and In Vivo

2006 ◽  
Vol 3 (1) ◽  
pp. 71-77 ◽  
Author(s):  
Yuta Inokuchi ◽  
Masamitsu Shimazawa ◽  
Yoshimi Nakajima ◽  
Shinsuke Suemori ◽  
Satoshi Mishima ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Water Soluble ◽  
Retinal Damage ◽  
Retinal Ganglion ◽  
Neuroprotective Effects ◽  
Brazilian Green Propolis

Propolis, a honeybee product, has gained popularity as a food and alternative medicine. Its constituents have been shown to exert pharmacological (anticancer, antimicrobial and anti-inflammatory) effects. We investigated whether Brazilian green propolis exerts neuroprotective effects in the retinain vitroand/orin vivo.In vitro, retinal damage was induced by 24 h hydrogen peroxide (H2O2) exposure, and cell viability was measured by Hoechst 33342 and YO-PRO-1 staining or by a resazurin–reduction assay. Propolis inhibited the neurotoxicity and apoptosis induced in cultured retinal ganglion cells (RGC-5, a rat ganglion cell line transformed using E1A virus) by 24 h H2O2 exposure. Propolis also inhibited the neurotoxicity induced in RGC-5 cultures by staurosporine. Regarding the possible underlying mechanism, in pig retina homogenates propolis protected against oxidative stress (lipid peroxidation), as also did trolox (water-soluble vitamin E). In micein vivo, propolis (100 mg kg−1; intraperitoneally administered four times) reduced the retinal damage (decrease in retinal ganglion cells and in thickness of inner plexiform layer) induced by intravitrealin vivo N-methyl-d-aspartate injection. These findings indicate that Brazilian green propolis has neuroprotective effects against retinal damage bothin vitroandin vivo, and that a propolis-induced inhibition of oxidative stress may be partly responsible for these neuroprotective effects.

Sign in / Sign up

Export Citation Format

Share Document