Methods of treating optic nerve diseases using neural progenitor cell growth factors
Optic nerve lamina region neural progenitor cells (ONLR-NPCs) are provided. Such cells secrete growth factors and survival factors that can be used in the treatment of optic nerve diseases, such as glaucoma. Also provided are methods of treating or preventing optic nerve diseases, such as glaucoma, using one or more factors secreted by ONLR-NPCs, combinations of factors secreted by ONLR-NPCs, or culture media conditioned by ONLR-NPCs.
1. A method of treating or preventing an optic nerve disease in a subject comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising one or more of:
(i) a population of optic nerve lamina region-neural progenitor cells (ONLR-NPCs),
(ii) ONLR-NPC conditioned media,
(iii) an ONLR-NPC lysate, and
thereby treating or preventing an optic nerve disease in the subject.
2. The method of claim 1 , wherein the optic nerve disease is selected from the group consisting of open-angle glaucoma, angle-closure glaucoma, optic nerve hypoplasia, optic nerve hypomyelination, regional axonal dysfunction, nonarteritic anterior ischemic optic neuropathy (NAION), and optic neuritis.
3. The method of claim 1 , wherein the composition is administered to the eye of the subject.
4. The method of claim 1 , wherein the composition is administered to the subject via one or more of topical application, subconjunctival injection, intravitreal injection, and retrobulbar injection.
5. The method of claim 1 , wherein the composition administered to the subject is a pharmaceutical formulation comprising a pharmaceutically acceptable carrier.
6. The method of claim 1 , wherein the subject is a human.
7. The method of claim 1 , wherein the ONLR-NPCs are nestin(+), SOX2(+), GFAP(+), NG2(−) cells.
8. The method of claim 1 , wherein the ONLR-NPCs are nestin(+), SOX2(+), GFAP(+), NG2(−), SOX1(+), vimentin(+), BDNF(+) cells.
9. The method of claim 1 , wherein the ONLR-NPCs express one or more of Latent Transforming Growth Factor-Beta 1 (TGF-β1), Connective Tissue Growth Factor (CTGF), Nerve Growth Factor (NGF), Fibroblast Growth Factor (FGF-1), Vascular Endothelial Growth Factor (VEGF), Mesenchymal Astrocyte Neurotrophic Factor (MANF) and Insulin-like Growth Factors-1 and -2 (IGF-1 and IGF-2).
10. The method of claim 1 , wherein the ONLR-NPCs express at least five growth factors selected from the group consisting of VGF, TGFβ1, LTBP1, LTBP2, PDGFB, CTGF, FGF11, NDNF, PDGFC, TGFβ2, NGF, FGF1, Midkine, VEGFA, MANF, IGF-1, and IGF-2.
11. The method of claim 1 , wherein the ONLR-NPCs express each of VGF, TGFβ1, LTBP1, LTBP2, PDGFB, CTGF, FGF11, NDNF, PDGFC, TGFβ2, NGF, FGF1, Midkine, VEGFA, MANF, IGF-1, and IGF-2.
12. The method of claim 1 , wherein the ONLR-NPCs express one or more proteins selected from the group consisting of Cell Growth Regulator with Ring Finger Domain 1, Dynein Regulatory Complex Subunit 4, Fibroblast Growth Factor 12, Fibroblast Growth Factor 14, Fibroblast Growth Factor Receptor 4, Growth Arrest and DNA Damage-inducible Protein GADD45 beta, Growth Factor Independent 1 Transcriptional Repressor, Growth Hormone Receptor, Placental Growth Factor, Platelet-derived Growth Factor D/Spinal Cord-Derived Growth Factor B, Platelet-derived Growth Factor Receptor-like Protein, Transforming Growth Factor beta-1 Proprotein, Transforming Growth Factor beta-1-induced Transcript 1 Protein, Upper Zone of Growth Plate and Cartilage Matrix Associated Protein, Vascular Endothelial Growth Factor C and UNC-13 Homolog C.
13. The method of claim 1 , wherein the ONLR-NPCs express each of Cell Growth Regulator with Ring Finger Domain 1, Dynein Regulatory Complex Subunit 4, Fibroblast Growth Factor 12, Fibroblast Growth Factor 14, Fibroblast Growth Factor Receptor 4, Growth Arrest and DNA Damage-inducible Protein GADD45 beta, Growth Factor Independent 1 Transcriptional Repressor, Growth Hormone Receptor, Placental Growth Factor, Platelet-derived Growth Factor D/Spinal Cord-Derived Growth Factor B, Platelet-derived Growth Factor Receptor-like Protein, Transforming Growth Factor beta-1 Proprotein, Transforming Growth Factor beta-1-induced Transcript 1 Protein, Upper Zone of Growth Plate and Cartilage Matrix Associated Protein, Vascular Endothelial Growth Factor C and UNC-13 Homolog C.
14. The method of claim 1 , wherein the composition comprising one or more factors secreted by ONLR-NPCs comprises one or more of Latent Transforming Growth Factor-Beta 1 (TGF-β1), Connective Tissue Growth Factor (CTGF), Nerve Growth Factor (NGF), Fibroblast Growth Factor (FGF-1), Vascular Endothelial Growth Factor (VEGF), Mesenchymal Astrocyte Neurotrophic Factor (MANF) and Insulin-like Growth Factors-1 and -2 (IGF-1 and IGF-2).
15. The method of claim 1 , wherein the composition comprising one or more factors secreted by ONLR-NPCs comprises each of Latent Transforming Growth Factor-Beta 1 (TGF-β1), Connective Tissue Growth Factor (CTGF), Nerve Growth Factor (NGF), Fibroblast Growth Factor (FGF-1), Vascular Endothelial Growth Factor (VEGF), Mesenchymal Astrocyte Neurotrophic Factor (MANF) and Insulin-like Growth Factors-1 and -2 (IGF-1 and IGF-2).
16. The method of claim 1 , wherein the composition comprising one or more factors secreted by ONLR-NPCs comprises at least five of growth factors selected from the group consisting of VGF, TGFβ1, LTBP1, LTBP2, PDGFB, CTGF, FGF11, NDNF, PDGFC, TGFβ2, NGF, FGF1, Midkine, VEGFA, MANF, IGF-1, and IGF-2.
17. The method of claim 1 , wherein the composition comprising one or more factors secreted by ONLR-NPCs comprises each of VGF, TGFβ1, LTBP1, LTBP2, PDGFB, CTGF, FGF11, NDNF, PDGFC, TGFβ2, NGF, FGF1, Midkine, VEGFA, MANF, IGF-1, and IGF-2.