PURPOSE: To evaluate the ability of mesenchymal stem cells (MSCs) engineered to produce and secrete brain-derived neurotrophic factor (BDNF) to protect retinal function and structure after intravitreal transplantation in a rat model of chronic ocular hypertension (COH). METHODS: COH was induced by laser cauterization of trabecular meshwork and episcleral veins in rat eyes. COH eyes received an intravitreal transplant of MSCs engineered to express BDNF and green fluorescent protein (BDNF-MSCs) or just GFP (GFP-MSCs). Computerized pupillometry and electroretinography (ERG) were performed to assess optic nerve and retinal function. Quantification of optic nerve damage was performed by counting retinal ganglion cells (RGCs) and evaluating optic nerve cross-sections. RESULTS: After transplantation into COH eyes, BDNF-MSCs preserved significantly more retina and optic nerve function than GFP-MSC-treated eyes when pupil light reflex (PLR) and ERG function were evaluated. PLR analysis showed significantly better function (P = 0.03) in BDNF-MSC-treated eyes (operated/control ratio = 63.00% ± 11.39%) than GFP-MSC-treated eyes (operated/control ratio = 31.81% ± 9.63%) at 42 days after surgery. The BDNF-MSC-transplanted eyes also displayed a greater level of RGC preservation than eyes that received the GFP-MSCs only (RGC cell counts: BDNF-MSC-treated COH eyes, 112.2 ± 19.39 cells/section; GFP-MSC-treated COH eyes, 52.21 ± 11.54 cells/section; P = 0.01). CONCLUSIONS: The authors have demonstrated that lentiviral-transduced BDNF-producing MSCs can survive in eyes with chronic hypertension and can provide retina and optic nerve functional and structural protection. Transplantation of BDNF-producing stem cells may be a viable treatment strategy for glaucoma.
PURPOSE: To evaluate the ability of mesenchymal stem cells (MSCs) engineered to produce and secrete brain-derived neurotrophic factor (BDNF) to protect retinal function and structure after intravitreal transplantation in a rat model of chronic ocular hypertension (COH). METHODS: COH was induced by laser cauterization of trabecular meshwork and episcleral veins in rat eyes. COH eyes received an intravitreal transplant of MSCs engineered to express BDNF and green fluorescent protein (BDNF-MSCs) or just GFP (GFP-MSCs). Computerized pupillometry and electroretinography (ERG) were performed to assess optic nerve and retinal function. Quantification of optic nerve damage was performed by counting retinal ganglion cells (RGCs) and evaluating optic nerve cross-sections. RESULTS: After transplantation into COH eyes, BDNF-MSCs preserved significantly more retina and optic nerve function than GFP-MSC-treated eyes when pupil light reflex (PLR) and ERG function were evaluated. PLR analysis showed significantly better function (P = 0.03) in BDNF-MSC-treated eyes (operated/control ratio = 63.00% ± 11.39%) than GFP-MSC-treated eyes (operated/control ratio = 31.81% ± 9.63%) at 42 days after surgery. The BDNF-MSC-transplanted eyes also displayed a greater level of RGC preservation than eyes that received the GFP-MSCs only (RGC cell counts: BDNF-MSC-treated COH eyes, 112.2 ± 19.39 cells/section; GFP-MSC-treated COH eyes, 52.21 ± 11.54 cells/section; P = 0.01). CONCLUSIONS: The authors have demonstrated that lentiviral-transduced BDNF-producing MSCs can survive in eyes with chronic hypertension and can provide retina and optic nerve functional and structural protection. Transplantation of BDNF-producing stem cells may be a viable treatment strategy for glaucoma.
Authors: Atsushi Otani; Michael Ian Dorrell; Karen Kinder; Stacey K Moreno; Steven Nusinowitz; Eyal Banin; John Heckenlively; Martin Friedlander Journal: J Clin Invest Date: 2004-09 Impact factor: 14.808
Authors: Yuehua Jiang; Dori Henderson; Mark Blackstad; Angel Chen; Robert F Miller; Catherine M Verfaillie Journal: Proc Natl Acad Sci U S A Date: 2003-08-18 Impact factor: 11.205
Authors: Brad Fortune; Bang V Bui; John C Morrison; Elaine C Johnson; Jin Dong; William O Cepurna; LiJun Jia; Stacey Barber; George A Cioffi Journal: Invest Ophthalmol Vis Sci Date: 2004-06 Impact factor: 4.799
Authors: Thomas V Johnson; Nicholas W DeKorver; Victoria A Levasseur; Andrew Osborne; Alessia Tassoni; Barbara Lorber; Janosch P Heller; Rafael Villasmil; Natalie D Bull; Keith R Martin; Stanislav I Tomarev Journal: Brain Date: 2013-10-30 Impact factor: 13.501
Authors: Wei Zhu; Oliver W Gramlich; Lauren Laboissonniere; Ankur Jain; Val C Sheffield; Jeffrey M Trimarchi; Budd A Tucker; Markus H Kuehn Journal: Proc Natl Acad Sci U S A Date: 2016-06-06 Impact factor: 11.205
Authors: Anup D Sharma; Pavel A Brodskiy; Emma M Petersen; Melih Dagdeviren; Eun-Ah Ye; Surya K Mallapragada; Donald Sakaguchi Journal: J Vis Exp Date: 2015-01-04 Impact factor: 1.355