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1 General aspects (0)   1.1 Epidemiology (8)   1.2 Population genetics (0)   1.3 Pathogenesis (4)   1.4 Quality of life (13)   1.5 Glaucomas as cause of blindness (5)   1.6 Prevention and screening (11) 2 Anatomical structures in glaucoma (0)   2.1 Conjunctiva (12)   2.2 Cornea (28)   2.3 Sclera (9)   2.4 Anterior chamber angle (8)   2.5 Meshwork (0)     2.5.1 Trabecular meshwork (9)     2.5.2 Schlemms canal (1)     2.5.3 Scleral outlet channels (0)   2.6 Aqueous humor dynamics (0)     2.6.1 Production (1)     2.6.2 Outflow (2)       2.6.2.1 Trabecular meshwork (4)       2.6.2.2 Uveoscleral (1)     2.6.3 Compostion (2)   2.7 Episcleral veins and venous pressure (0)   2.8 Iris (2)   2.9 Ciliary body (1)   2.10 Lens (1)   2.11 Vitreous body (1)   2.12 Choroid, peripapillary choroid, peripapillary atrophy (11)   2.13 Retina and retinal nerve fibre layer (30)   2.14 Optic disc (28)   2.15 Optic nerve (3)   2.16 Chiasma and retrochiasmal central nervous system (11)   2.17 Stem cells (1)   2.20 Other (0) 3 Laboratory methods (0)   3.1 Microscopy (4)   3.2 Electron microscopy (0)   3.3 Immunohistochemistry (1)   3.4 Molecular genetics (0)     3.4.1 Linkage studies (1)     3.4.2 Gene studies (27)   3.5 Molecular biology incl. 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Filtering surgery (0)     12.8.1 Without tube implant (10)     12.8.2 With tube implant or other drainage devices (42)     12.8.3 Non-perforating (4)     12.8.4 Using laser (0)     12.8.5 Other (0)     12.8.10 Woundhealing antifibrosis (15)     12.8.11 Complications, endophthalmitis (14)   12.9 Trabeculotomy, goniotomy (5)   12.10 Cyclodestruction (5)   12.11 Cyclodialysis (0)   12.12 Cataract extraction (0)     12.12.1 Intracapsular (0)     12.12.2 Extracapsular (0)     12.12.3 Phacoemulsification (12)   12.14 Combined cataract extraction and glaucoma surgery (0)     12.14.1 Intracapsular (0)     12.14.2 Extracapsular (0)     12.14.3 Phacoemulsification (10)   12.15 Capsulotomy (0)   12.16 Vitrectomy (0)   12.17 Anesthesia (2)   12.20 Other (2) 13 Therapeutic prognosis and outcome (0)   13.1 Prognostic factors (1)   13.2 Outcome (2)     13.2.1 IOP (0)     13.2.2 Visual field (0)       13.2.2.1 Progression (0)       13.2.2.2 Improvement (0)     13.2.3 Other (0) 14 Costing studies; pharmacoeconomics (6) 15 Miscellaneous (20)

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Abstract #61741 Published in IGR 17-1

Transplantation of Human Neural Progenitor Cells Expressing IGF-1 Enhances Retinal Ganglion Cell Survival

Ma J; Guo C; Sun Y; Liao T; Beattie U; López FJ; Chen DF; Lashkari K
PLoS ONE 2015; 10: e0125695

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We have previously characterized human neuronal progenitor cells (hNP) that can adopt a retinal ganglion cell (RGC)-like morphology within the RGC and nerve fiber layers of the retina. In an effort to determine whether hNPs could be used a candidate cells for targeted delivery of neurotrophic factors (NTFs), we evaluated whether hNPs transfected with an vector that expresses IGF-1 in the form of a fusion protein with tdTomato (TD), would increase RGC survival in vitro and confer neuroprotective effects in a mouse model of glaucoma. RGCs co-cultured with hNPIGF-TD cells displayed enhanced survival, and increased neurite extension and branching as compared to hNPTD or untransfected hNP cells. Application of various IGF-1 signaling blockers or IGF-1 receptor antagonists abrogated these effects. In vivo, using a model of glaucoma we showed that IOP elevation led to reductions in retinal RGC count. In this model, evaluation of retinal flatmounts and optic nerve cross sections indicated that only hNPIGF-TD cells effectively reduced RGC death and showed a trend to improve optic nerve axonal loss. RT-PCR analysis of retina lysates over time showed that the neurotrophic effects of IGF-1 were also attributed to down-regulation of inflammatory and to some extent, angiogenic pathways. This study shows that neuronal progenitor cells that hone into the RGC and nerve fiber layers may be used as vehicles for local production and delivery of a desired NTF. Transplantation of hNPIGF-TD cells improves RGC survival in vitro and protects against RGC loss in a rodent model of glaucoma. Our findings have provided experimental evidence and form the basis for applying cell-based strategies for local delivery of NTFs into the retina. Application of cell-based delivery may be extended to other disease conditions beyond glaucoma.

Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, 02114, MA, United States of America.

Full article

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Classification:

2.17 Stem cells (Part of: 2 Anatomical structures in glaucoma)
11.8 Neuroprotection (Part of: 11 Medical treatment)
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)

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