Ophthalmology
 

     In recent years the stem cell science has increasingly focused on mitigating the loss of vision through Ophthalmology. Cell based therapies are showing tremendous promise in mitigating many acquired and hereditary vision problems. Age Related Macular Degeneration in particular is under scrutiny as a condition that is likely to respond to adult mesenchymal cell therapy.

Ophthalmology and Cell Surgical Network

     At Cell Surgical Network, we have been studying the effects of SVF (rich in mesenchymal stem cells and growth factors) on various ophthalmologic conditions including Macular degeneration, retinitis pigmentosa, diabetic retinopathy, retinal detachments, Leber’s optic neuropathy and optic neuritis. In collaboration with our ophthalmology consultants we have designed protocols for visual loss conditions that emphasize safety and efficacy.  The deployment protocol performed under local anesthesia is all done as an outpatient at the time of SVF harvesting and procurement. The entire cellular surgical procedure takes approximately 3 hours.

Ophthalmology Call to Action

     We care about our Ophthalmology patients at the Cell Surgical Network and take pride in the time we provide to our patients to deploy the best protocols to help our patients achieve their goals. By filling out Candidate Application we will answer the questions and concerns you may have about Cell Surgical Network protocols for Ophthalmology.

 
CANDIDATE APPLICATION
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Cell Surgical Network Study for Stromal Vascular Fraction Registered by ClinicalTrials.gov

Rancho Mirage, CA (PRWEB) October 14, 2013

Clinicaltrials.gov, a service of the U.S. National Institutes of Health has registered on their public site an IRB approved safety study from the Cell Surgical Network, Inc.. This study is available for patients with various degenerative and inflammatory conditions to undergo Stromal Vascular Fraction deployment for the evaluation and for the advancement of future stem cell therapy procedures. Stromal Vascular Fraction is rich in autologous adipose derived stem cells and growth factors.

Stromal Vascular Fraction (SVF) is obtained by lipo-harvesting, procurement, and lipo-transfer as a same day operative procedure to provide therapy to patients with various degenerative and inflammatory diseases. Patients must be 16 years or older, male or female and have a degenerative disease or inflammatory disease that meets criteria for treatment under the IRB which includes: Arthritis, Auto-immune disease, COPD, Cardiomyopathy, Peyronies Disease, Interstitial Cystitis, Erectile Dysfunction, and Neurodegenerative disease such as Parkinson’s, ALS, Neuropathy. Patients must be healthy enough to tolerate a local anesthetic, must not have active cancer or infections.

Dr. Elliot Lander, and Dr. Mark Berman, founders of the Cell Surgical Network Inc. will conduct the study: “Ever since our inception, it’s been our goal to maintain transparency during our investigations. With a closed surgical procedure we can provide effective safety studies and evolve good empirical data that will allow us and others to ultimately refine our protocols,” says Dr. Berman.

The purpose of the safety study is to evaluate for any adverse effects that may be related to the administration and reception of autologous adipose derived stromal vascular fraction (SVF). Secondarily, the study monitors the results of subjective and objective findings as it applies to the non-blinded deployment of autologous SVF for various inflammatory and/or degenerative conditions including select orthopedic, neurologic, urologic and cardio-pulmonary conditions. SVF deployments include intra-venous, intra-articular, and soft tissue injections.

Outcome measures will include the number of participants with adverse events related to either SVF deployment or the lipo-harvesting procedure. Interested patients should contact the treatment center by phone: 800-231-0407 or via email: info(at)cellsurgicalnetwork(dot)com

About Cell Surgical Network:

The affiliates of the Cell Surgical Network (CSN) are devoted to advancing access and quality care in the area of adult stem cell regenerative medicine in order to help people suffering from a variety of inflammatory and degenerative conditions. The Cell Surgical Network was founded nearly two years after the formation of the California Stem Cell Treatment Center (founded in 2010). Affiliate members are generally made up of multi-state and international teams of multidisciplinary physicians in order to best assess and provide care for our patients. The Cell Surgical Network emphasizes quality and is highly committed to clinical research and the advancement of regenerative medicine.

 
Regenerative Therapeutic Potential of Adipose Stromal Cells in Early Stage Diabetic Retinopathy
 
Gangaraju Rajashekhar, Ahmed Ramadan, Chandrika Abburi, Breedge Callaghan, Dmitry O. Traktuev, Carmella Evans-Molina, Raj Maturi,  Alon Harris, Timothy S. Kern,  Keith L. March
 
Indiana Center for Vascular Biology & Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America, Eugene and Marilyn Glick Eye nInstitute, Indiana University School of Medicine, Indianapolis, Indiana, United States of America, Vascular and Cardiac Center for Adult Stem Cell Therapy, Indiana University School of Medicine, Indianapolis, Indiana, United States of America, VA Center for Regenerative Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America, Department of Cellular & Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America, Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Indiana, United States of America, Midwest Eye Institute, Indianapolis, Indiana, United States oAmerica, Departments of Medicine and Ophthalmology, Case Western Reserve University, Cleveland, Ohio, United States of America
 
Abstract
Diabetic retinopathy (DR) is the leading cause of blindness in working-age adults. Early stage DR involves inflammation,
vascular leakage, apoptosis of vascular cells and neurodegeneration. In this study, we hypothesized that cells derived from
the stromal fraction of adipose tissue (ASC) could therapeutically rescue early stage DR features. Streptozotocin (STZ)
induced diabetic athymic nude rats received single intravitreal injection of human ASC into one eye and saline into the
other eye. Two months post onset of diabetes, administration of ASC significantly improved ‘‘b’’ wave amplitude (as
measured by electroretinogram) within 1–3 weeks of injection compared to saline treated diabetic eyes. Subsequently,
retinal histopathological evaluation revealed a significant decrease in vascular leakage and apoptotic cells around the retinal
vessels in the diabetic eyes that received ASC compared to the eyes that received saline injection. In addition, molecular
analyses have shown down-regulation in inflammatory gene expression in diabetic retina that received ASC compared to
eyes that received saline. Interestingly, ASC were found to be localized near retinal vessels at higher densities than seen in
age matched non-diabetic retina that received ASC.
In vitro
, ASC displayed sustained proliferation and decreased apoptosis
under hyperglycemic stress. In addition, ASC in co-culture with retinal endothelial cells enhance endothelial survival and
collaborate to form vascular networks. Taken together, our findings suggest that ASC are able to rescue the neural retina
from hyperglycemia-induced degeneration, resulting in importantly improved visual function. Our pre-clinical studies
support the translational development of adipose stem cell-based therapy for DR to address both retinal capillary and
neurodegeneration.
 
 


Cell Therapy Applications for Retinal Vascular Diseases: Diabetic Retinopathy and Retinal Vein Occlusion.


 Invest Ophthalmol Vis Sci. 2016 Apr 1;57(5):ORSFj1-ORSFj10. doi: 10.1167/iovs.15-17594.

Author: Park SS.

Abstract
 
Retinal vascular conditions, such as diabetic retinopathy and retinal vein occlusion, remain leading causes of vision loss. No therapy exists to restore vision loss resulting from retinal ischemia and associated retinal degeneration. Tissue regeneration is possible with cell therapy. The goal would be to restore or replace the damaged retinal vasculature and the retinal neurons that are damaged and/or degenerating from the hypoxic insult. Currently, various adult cell therapies have been explored as potential treatment. They include mesenchymal stem cells, vascular precursor cells (i.e., CD34+ cells, hematopoietic cells or endothelial progenitor cells), and adipose stromal cells. Preclinical studies show that all these cells have a paracrine trophic effect on damaged ischemic tissue, leading to tissue preservation. Endothelial progenitor cells and adipose stromal cells integrate into the damaged retinal vascular wall in preclinical models of diabetic retinopathy and ischemia-reperfusion injury. Mesenchymal stem cells do not integrate as readily but appear to have a primary paracrine trophic effect. Early phase clinical trials have been initiated and ongoing using mesenchymal stem cells or autologous bone marrow CD34+ cells injected intravitreally as potential therapy for diabetic retinopathy or retinal vein occlusion. Adipose stromal cells or pluripotent stem cells differentiated into endothelial colony-forming cells have been explored in preclinical studies and show promise as possible therapies for retinal vascular disorders. The relative safety or efficacy of these various cell therapies for treating retinal vascular disorders have yet to be determined.
 

 Stem Cell Therapies for Reversing Vision Loss.

Trends Biotechnol. 2017 Jul 24. pii: S0167-7799(17)30165-8. doi: 10.1016/j.tibtech.2017.06.016

Authors: Higuchi A, Kumar SS, Benelli G, Alarfaj AA, Munusamy MA, Umezawa A, Murugan K.

Abstract

 

Current clinical trials that evaluate human pluripotent stem cell (hPSC)-based therapies predominantly target treating macular degeneration of the eyes because the eye is an isolated tissue that is naturally weakly immunogenic. Here, we discuss current bioengineering approaches and biomaterial usage in combination with stem cell therapy for macular degeneration disease treatment. Retinal pigment epithelium (RPE) differentiated from hPSCs is typically used in most clinical trials for treating patients, whereas bone marrow mononuclear cells (BMNCs) or mesenchymal stem cells (MSCs) are intravitreally transplanted, undifferentiated, into patient eyes. We also discuss reported negative effects of stem cell therapy, such as patients becoming blind following transplantation of adipose-derived stem cells, which are increasingly used by 'stem-cell clinics'.

 

 


Progress of mesenchymal stem cell therapy for neural and retinal diseases.


World J Stem Cells. 2014 Apr 26;6(2):111-9. doi: 10.4252/wjsc.v6.i2.111.

Ng TK, Fortino VR, Pelaez D1, Cheung HS.Tsz Kin Ng, Daniel Pelaez, Herman S Cheung,

Abstract
 

Complex circuitry and limited regenerative power make central nervous system (CNS) disorders the most challenging and difficult for functional repair. With elusive disease mechanisms, traditional surgical and medical interventions merely slow down the progression of the neurodegenerative diseases. However, the number of neurons still diminishes in many patients. Recently, stem cell therapy has been proposed as a viable option. Mesenchymal stem cells (MSCs), a widely-studied human adult stem cell population, have been discovered for more than 20 years. MSCs have been found all over the body and can be conveniently obtained from different accessible tissues: bone marrow, blood, and adipose and dental tissue. MSCs have high proliferative and differentiation abilities, providing an inexhaustible source of neurons and glia for cell replacement therapy. Moreover, MSCs also show neuroprotective effects without any genetic modification or reprogramming. In addition, the extraordinary immunomodulatory properties of MSCs enable autologous and heterologous transplantation. These qualities heighten the clinical applicability of MSCs when dealing with the pathologies of CNS disorders. Here, we summarize the latest progress of MSC experimental research as well as human clinical trials for neural and retinal diseases. This review article will focus on multiple sclerosis, spinal cord injury, autism, glaucoma, retinitis pigmentosa and age-related macular degeneration.

 

Mesenchymal stem cells: new players in retinopathy therapy.
Authors: Rajashekhar G1.

2014 Apr 24;5:59. doi: 10.3389/fendo.2014.00059. eCollection 2014.

Abstract

Retinopathies in human and animal models have shown to occur through loss of pericytes resulting in edema formation, excessive immature retinal angiogenesis, and neuronal apoptosis eventually leading to blindness. In recent years, the concept of regenerating terminally differentiated organs with a cell-based therapy has evolved. The cells used in these approaches are diverse and include tissue-specific endogenous stem cells, endothelial progenitor (EPC), embryonic stem cells, induced pluripotent stem cells (iPSC) and mesenchymal stem cells (MSC). Recently, MSC derived from the stromal fraction of adipose tissue have been shown to possess pluripotent differentiation potential in vitro. These adipose stromal cells (ASC) have been differentiated in a number of laboratories to osteogenic, myogenic, vascular, and adipocytic cell phenotypes. In vivo, ASC have been shown to have functional and phenotypic overlap with pericytes lining microvessels in adipose tissues. Furthermore, these cells either in paracrine mode or physical proximity with endothelial cells, promoted angiogenesis, improved ischemia-reperfusion, protected from myocardial infarction, and were neuroprotective. Owing to the easy isolation procedure and abundant supply, fat-derived ASC are a more preferred source of autologous mesenchymal cells compared to bone marrow MSC. In this review, we present evidence that these readily available ASC from minimally invasive liposuction will facilitate translation of ASC research into patients with retinal diseases in the near future.

PMID: 24795699
 
Stromal vascular fraction: A regenerative reality? Part 1: Current concepts and review of the literature

2016 Feb;69(2):170-9. doi: 10.1016/j.bjps.2015.10.015. Epub 2015 Oct 31.
International Journal of Surgical Reconstruction

Abstract
Summary

Stromal Vascular Fraction (SVF) is a heterogeneous collection of cells contained within adipose tissue that is traditionally isolated using enzymes such as collagenase. With the removal of adipose cells, connective tissue and blood from lipoaspirate, comes the SVF, a mix including mesenchymal stem cells, endothelial precursor cells, T regulatory cells, macrophages, smooth muscle cells, pericytes and preadipocytes. In part 1 of our 2-part series, we review the literature with regards to the intensifying interest that has shifted toward this mixture of cells, particularly due to its component synergy and translational potential. Trials assessing the regenerative potential of cultured Adipose Derived Stem Cells (ADSCs) and SVF demonstrate that SVF is comparably effective in treating conditions ranging from radiation injuries, burn wounds and diabetes, amongst others. Aside from their use in chronic conditions, SVF enrichment of fat grafts has proven a major advance in maintaining fat graft volume and viability. Many SVF studies are currently in preclinical phases or are moving to human trials. Overall, regenerative cell therapy based on SVF is at an early investigative stage but its potential for clinical application is enormous.

 

Stromal vascular fraction: A regenerative reality? Part 2: Mechanisms of regenerative action.
Authors: Andrew Nguyen,James Guo, Derek A. Banyard, Darya Fadavi, Jason D. Toranto, Garrett A. Wirth, Keyianoosh Z. Paydar, Gregory R.D. Evansc, Alan D. Widgerow

2016 Feb;69(2):180-8. doi: 10.1016/j.bjps.2015.10.014. Epub 2015 Oct 24.
International Journal of Surgical Reconstruction

Abstract
Summary

Adipose tissue is a rich source of cells with emerging promise for tissue engineering and regenerative medicine. The stromal vascular fraction (SVF), in particular, is an eclectic composite of cells with progenitor activity that includes preadipocytes, mesenchymal stem cells, pericytes, endothelial cells, and macrophages. SVF has enormous potential for therapeutic application and is being investigated for multiple clinical indications including lipotransfer, diabetes-related complications, nerve regeneration, burn wounds and numerous others. In Part 2 of our review, we explore the basic science behind the regenerative success of the SVF and discuss significant mechanisms that are at play. The existing literature suggests that angiogenesis, immunomodulation, differentiation, and extracellular matrix secretion are the main avenues through which regeneration and healing is achieved by the stromal vascular fraction.

 

Current approaches and future prospects for stem cell rescue and regeneration of the retina and optic nerve.
Authors: Dahlmann-Noor AVijay SJayaram HLimb AKhaw PT.

Source: UCL Partners AHSC, London, United Kingdom.

Abstract

The 3 most common causes of visual impairment and legal blindness in developed countries (age-related macular degeneration, glaucoma, and diabetic retinopathy) share 1 end point: the loss of neural cells of the eye. Although recent treatment advances can slow down the progression of these conditions, many individuals still suffer irreversible loss of vision. Research is aimed at developing new treatment strategies to rescue damaged photoreceptors and retinal ganglion cells (RGC) and to replace lost cells by transplant. The neuroprotective and regenerative potential of stem and progenitor cells from a variety of sources has been explored in models of retinal disease and ganglion cell loss. Continuous intraocular delivery of neurotrophic factors via stem cells (SC) slows down photoreceptor cells and RGC loss in experimental models. Following intraocular transplantation, SC are capable of expressing proteins and of developing a morphology characteristic of photoreceptors or RGC. Recently, recovery of vision has been achieved for the first time in a rodent model of retinal dystrophy, using embryonic SC differentiated into photoreceptors prior to transplant. This indicates that clinically significant synapse formation and acquisition of the functional properties of retinal neurons, and restoration of vision, are distinct future possibilities.

PMID:20648090[PubMed – indexed for MEDLINE]

Clin Exp Optom. 2008 Jan;91(1):78-84.

 

Stem Cell Therapies in Retinal Disorders.
Authors: Garg A, Yang J, Lee W, Tsang SH.

Abstract

Stem cell therapy has long been considered a promising mode of treatment for retinal conditions. While human embryonic stem cells (ESCs) have provided the precedent for regenerative medicine, the development of induced pluripotent stem cells (iPSCs) revolutionized this field. iPSCs allow for the development of many types of retinal cells, including those of the retinal pigment epithelium, photoreceptors, and ganglion cells, and can model polygenic diseases such as age-related macular degeneration. Cellular programming and reprogramming technology is especially useful in retinal diseases, as it allows for the study of living cells that have genetic variants that are specific to patients' diseases. Since iPSCs are a self-renewing resource, scientists can experiment with an unlimited number of pluripotent cells to perfect the process of targeted differentiation, transplantation, and more, for personalized medicine. Challenges in the use of stem cells are present from the scientific, ethical, and political realms. These include transplant complications leading to anatomically incorrect placement, concern for tumorigenesis, and incomplete targeting of differentiation leading to contamination by different types of cells. Despite these limitations, human ESCs and iPSCs specific to individual patients can revolutionize the study of retinal disease and may be effective therapies for conditions currently considered incurable.

PMID: 28157165
 

A review of the potential to restore vision with stem cells.
Authors: Mooney ILaMotte J.

Source: Southern California College of Optometry, Fullerton, California 92831, USA.

Abstract

Vision research involving stem cells is a rapidly evolving field. Animal experiments have shown that in response to environmental cues, stem cells can repopulate damaged retinas, regrow neuronal axons, repair higher cortical pathways, and restore pupil reflexes, light responses and basic pattern recognition. Viable corneas have been grown from stem cells and transplanted into humans. Similarly, human trials to repair damaged retinas in retinitis pigmentosa and age-related macular degeneration patients have produced preliminary successes. This review attempts to place the collective contributions toward stem cell/vision research into a broader clinical model of how stem cells might ultimately be used to restore the entire visual pathway.

PMID:18045253[PubMed – indexed for MEDLINE]

 

Stem cell-based therapeutic applications in retinal degenerative diseases.
Authors: Huang YEnzmann VIldstad ST.

Source: Institute for Cellular Therapeutics, University of Louisville, 570 S. Preston Street, Suite 404, Louisville, KY 40202-1760, USA.

Abstract

Retinal degenerative diseases that target photoreceptors or the adjacent retinal pigment epithelium (RPE) affect millions of people worldwide. Retinaldegeneration (RD) is found in many different forms of retinal diseases including retinitis pigmentosa (RP), age-related macular degeneration (AMD), diabetic retinopathy, cataracts, and glaucoma. Effective treatment for retinal degeneration has been widely investigated. Gene-replacement therapy has been shown to improve visual function in inherited retinal disease. However, this treatment was less effective with advanced disease. Stem cell-based therapy is being pursued as a potential alternative approach in the treatment of retinal degenerative diseases. In this review, we will focus onstem cell-based therapies in the pipeline and summarize progress in treatment of retinal degenerative disease.

PMID:20859770[PubMed – indexed for MEDLINE]PMCID:PMC3408315

Can J Ophthalmol. 2010 Aug;45(4):333-41. doi: 10.3129/i10-077.

 

Stem cell treatment of degenerative eye disease.
Authors: Mead B, Berry M, Logan A, Scott RA, Leadbeater W, Scheven BA.

Abstract

Stem cell therapies are being explored extensively as treatments for degenerative eye disease, either for replacing lost neurons, restoring neural circuits or, based on more recent evidence, as paracrine-mediated therapies in which stem cell-derived trophic factors protect compromised endogenous retinal neurons from death and induce the growth of new connections. Retinal progenitor phenotypes induced from embryonic stem cells/induced pluripotent stem cells (ESCs/iPSCs) and endogenous retinal stem cells may replace lost photoreceptors and retinal pigment epithelial (RPE) cells and restore vision in the diseased eye, whereas treatment of injured retinal ganglion cells (RGCs) has so far been reliant on mesenchymal stem cells (MSC). Here, we review the properties of non-retinal-derived adult stem cells, in particular neural stem cells (NSCs), MSC derived from bone marrow (BMSC), adipose tissues (ADSC) and dental pulp (DPSC), together with ESC/iPSC and discuss and compare their potential advantages as therapies designed to provide trophic support, repair and replacement of retinal neurons, RPE and glia in degenerative retinal diseases. We conclude that ESCs/iPSCs have the potential to replace lost retinal cells, whereas MSC may be a useful source of paracrine factors that protect RGC and stimulate regeneration of their axons in the optic nerve in degenerate eye disease. NSC may have potential as both a source of replacement cells and also as mediators of paracrine treatment.

 

Ocular Stem Cell Research from Basic Science to Clinical Application: A Report from Zhongshan Ophthalmic Center Ocular Stem Cell Symposium.
Authors: Ouyang H, Goldberg JL, Chen S, Li W, Xu GT, Li W, Zhang K, Nussenblatt RB, Liu Y, Xie T, Chan CC, Zack DJ.

Abstract

Stem cells hold promise for treating a wide variety of diseases, including degenerative disorders of the eye. The eye is an ideal organ for stem cell therapy because of its relative immunological privilege, surgical accessibility, and its being a self-contained system. The eye also has many potential target diseases amenable to stem cell-based treatment, such as corneal limbal stem cell deficiency, glaucoma, age-related macular degeneration (AMD), and retinitis pigmentosa (RP). Among them, AMD and glaucoma are the two most common diseases, affecting over 200 million people worldwide. Recent results on the clinical trial of retinal pigment epithelial (RPE) cells from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) in treating dry AMD and Stargardt's disease in the US, Japan, England, and China have generated great excitement and hope. This marks the beginning of the ocular stem cell therapy era. The recent Zhongshan Ophthalmic Center Ocular Stem Cell Symposium discussed the potential applications of various stem cell types in stem cell-based therapies, drug discoveries and tissue engineering for treating ocular diseases.

PMID: 27102165
 
 

Stem cells in retinal regeneration: past, present and future.
Authors: Ramsden CM1, Powner MB, Carr AJ, Smart MJ, da Cruz L, Coffey PJ.

Abstract

Stem cell therapy for retinal disease is under way, and several clinical trials are currently recruiting. These trials use human embryonic, foetal and umbilical cord tissue-derived stem cells and bone marrow-derived stem cells to treat visual disorders such as age-related macular degeneration, Stargardt's disease and retinitis pigmentosa. Over a decade of analysing the developmental cues involved in retinal generation and stem cell biology, coupled with extensive surgical research, have yielded differing cellular approaches to tackle these retinopathies. Here, we review these various stem cell-based approaches for treating retinal diseases and discuss future directions and challenges for the field.

 
PMID: 23715550
 

Stem Cell-Based Therapy for Diseases of the Retinal Pigment Epithelium: From Bench to Bedside.
Authors: Sachdeva MM1, Eliott D1.

Abstract

Age-related macular degeneration (AMD) represents a leading cause of blindness in the elderly, and Stargardt's macular dystrophy (SMD) is the most common form of juvenile-onset macular degeneration. Dry AMD and SMD share an underlying pathophysiology, namely dysfunction and ultimately loss of the retinal pigment epithelium (RPE), suggesting that RPE transplantation may offer a potential treatment strategy for both patient populations. Stem cells have emerged as a promising source of replacement RPE. During the past 15 years, extraordinary strides have been made in the identification, characterization, and differentiation of stem cells. Recently, this large body of basic science and preclinical research has been translated to patient care with the publication of results from Phase 1/2 trials demonstrating safety of transplantation of human embryonic stem cell (hESC)-derived RPE into patients with AMD and SMD. While significant challenges remain before dry AMD and SMD become treatable diseases, the goal has become more tangible.

PMID: 26959126

 
 

Neuroprotective effects of intravitreal mesenchymal stem cell transplantation in experimental glaucoma.
Authors: Johnson TV, Bull ND, Hunt DP, Marina N, Tomarev SI, Martin KR.

Source: Centre for Brain Repair, University of Cambridge, Cambridge, United Kingdom.

Abstract

Purpose. Retrograde neurotrophic factor transport blockade has been implicated in the pathophysiology of glaucoma. Stem cell transplantation appears to ameliorate some neurodegenerative conditions in the brain and spinal cord, in part by neurotrophic factor secretion. The present study was conducted to determine whether local or systemic bone marrow-derived mesenchymal stem cell (MSC) transplantation can confer neuroprotection in a rat model of laser-induced ocular hypertensive glaucoma. Methods. MSCs were isolated from the bone marrow of adult wild-type and transgenic rats that ubiquitously express green fluorescent protein. MSCs were transplanted intravitreally 1 week before, or intravenously on the day of, ocular hypertension induction by laser photocoagulation of the trabecular meshwork. Ocular MSC localization and integration were determined by immunohistochemistry. Optic nerve damage was quantified by counting axons within optic nerve cross-sections 4 weeks after laser treatment. Results. After intravitreal transplantation, MSCs survived for at least 5 weeks. Cells were found mainly in the vitreous cavity, though a small proportion of discrete cells migrated into the host retina. Intravitreal MSC transplantation resulted in a statistically significant increase in overall RGC axon survival and a significant decrease in the rate of RGC axon loss normalized to cumulative intraocular pressure exposure. After intravenous transplantation, MSCs did not migrate to the injured eye. Intravenous transplantation had no effect on optic nerve damage. Conclusions. Local, but not systemic, transplantation of MSCs was neuroprotective in a rat glaucoma model. Autologous intravitreal transplantation of MSCs should be investigated further as a potential neuroprotective therapy for glaucoma.

Invest Ophthalmol Vis Sci. 2007 Jan;48(1):446-54.

 
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