Neuroprotección de las células ganglionares de la retina
ISSN: 0365-6691
Year of publication: 2003
Volume: 78
Issue: 3
Pages: 151-157
Type: Article
More publications in: Archivos de la Sociedad Española de Oftalmologia
Abstract
Purpose: To study the pig retinal ganglion cell (RGC) survival in culture, analysing the possible neuroprotective effect of retinal Müller glia (RMG) and brain-derived neurotrophic factor (BDNF). Methods: Adult pig retina were dissociated and cultured under different conditions: 1) on laminin/poly-D-lysine-coated coverslips in chemically defined medium (CDM); 2) on laminin/poly-D-lysine-coated coverslips in CMD supplemented with BDNF; 3) on confluent monolayer cultures of RMG in CDM; 4) on laminin/poly-D-lysine substrate in conditioned medium obtained from RMG. RGCs were identified by immunocytochemistry using antibody against 68 kDa neurofilament and observed under an fluorescent microscope. RGCs were classified on the basis of the size, number and length of neurites, and their survival was assayed for each treatment. Results: Confluent RMG substrates and RMG conditioned medium significantly increased the survival of cultured pig RGC. Moreover these two conditions increased the mean area of RGCs and enhanced neurite growth and elongation. Addition of BDNF to culture medium did not modify survival but increased RGC size, neurite number and neurite length. Conclusions: These findings demonstrate that factor(s) secreted by RMG exert beneficial effects on adult RGC survival and neurite regeneration in vitro, and might constitute important agent(s) for RGC neuroprotection. BDNF also increases the mean area of RGCs and enhances neurite growth but it does not increase the survival of RGCs.
Bibliographic References
- García-Valenzuela, E, Egorczyca, W, Darzynkiewicz, Z, Sharma, SC. (1994). Apoptosis in adult retinal ganglion cells after axotomy. J Neurobiol. 25. 431-438
- Quigley, HA, Nickells, RW, Kerrian, LA, Pease, ME, Thibant, DJ. (1995). Retinal ganglion cell death in experimental glaucoma and after axotomy occurs by apoptosis. Invest Ophthalmol Vis Sci. 36. 774-786
- Chen, H, Weber, AJ. (2001). BDNF enhances retinal ganglion cell survival in cats with optic nerve damage. Invest Ophthalmol Vis Sci. 42. 966-974
- Mey, J, Thanos, S. (1993). Intravitreal injections of neurotrophic factors support the survival of axotomized retinal ganglion cells in adult rats in vivo. Brain Res. 602. 304-317
- Glovinsky, Y, Quigley, HA, Pease, ME. (1993). Foveal ganglion cell loss is size dependent in experimental glaucoma. Invest Ophthalmol Vis Sci. 34. 395-400
- Peinado-Ramón, P, Salvador, M, Villegas-Pérez, MP, Vidal-Sanz, M. (1996). Effects of axotomy and intraocular administration of NT-4, NT-3 and brain-derived neurotrophic factor on the survival of adult rat retinal ganglion cells: A cuantitative in vivo study. Invest Ophthalmol Vis Sci. 37. 489-500
- Ko, ML, Hu, DN, Ritch, R, Sharma, SC. (2000). The combined effect of brain derived neurotrophic factor and a free radical scavenger in experimental glaucoma. Invest Ophthalmol Vis Sci. 41. 2967-2971
- Heidinger, V, Hicks, D, Sahel, J, Dreyfus, H. (1999). Ability of retinal Müller glial cells to protect neurons against excitotoxicity in vitro depends upon maduration and neuron-glial interactions. Glia. 25. 229-239
- Cao, W, Wen, R, Li, F, Cheng, T, Steinberg, RH. (1997). Induction of basic fibroblast growth factor mRNA by basic fibroblast growth factor in Müller cells. Invest Ophthalmol Vis Sci. 38. 1358-1366
- Chun, MH, Ju, WK, Kim, KY, Lee, MY, Hofmann, HD, Kirsch, M. (2000). Upregulation of ciliary neurotrophic factor in reactive Müller cells in the rat retina following optic nerve transection. Brain Res. 868. 358-362
- Gaudin, C, Forster, V, Sahel, JA, Dreyfus, H, Hicks, D. (1996). Survival and regeneration of adult human and other mammalian photoreceptors in culture. Invest Ophthalmol Vis Sci. 37. 2258-2268
- Guidry, C. (1996). Isolation and characterization of porcine Muller cells: Myofibroblastic dedifferentiation in culture. Invest Ophthalmol Vis Sci. 37. 740-752
- Pease, ME, McKinnon, SJ, Quigley, HA, Kerrigan-Baumrind, LA, Zack, DJ. (2000). Obstructed axonal transport of BDNF and its receptor TrkB in experimental glaucoma. Invest Ophthalmol Vis Sci. 41. 764-774
- Herzog, KH, von Bartheld, CS. (1998). Contributions of the optic tectum and the retina as sources of brain-derived neurotrophic factor for retinal ganglion cells in the chick embryo. J Neurosci. 18. 2891-2906
- Vecino, E, Garcia-Crespo, D, Garcia, M, Martinez-Millan, L, Sharma, SC, Carrascal, E. (2002). Rat retinal ganglion cells co-express brain derived neurotrophic factor (BDNF) and its receptor TrkB. Vision Res. 42. 151-157
- Frank, L, Ventimiglia, R, Anderson, K, Lindsay, RM, Rudge, JS. (1996). BDNF down-regulates neurotrophin responsiveness, trkB protein and trkB mRNA levels in cultured rat hippocampal neurons. Eur J Neurosci. 8. 1220-1230
- Luo, X, Lambrou, GN, Sahel, JA, Hicks, D. (2001). Hypoglycemia induces general neuronal death, whereas hypoxia and glutamate transport blockade lead to selective retinal ganglion cell death in vitro. Invest Ophthalmol Vis Sci. 42. 2695-2705
- Luo, X, Heidinger, V, Picaud, S. (2001). Selective excitotoxic degeneration of adult pig retinal ganglion cells in vitro. Invest Ophthalmol Vis Sci. 42. 1096-1106
- Kashiwagi, F, Kashiwagi, K, Iizuka, Y, Tsukahara, S. (2000). Effects of brain-derived neurotrophic factor and neurotrophin-4 on isolated cultured retinal ganglion cells: evaluation by flow cytometry. Invest Ophthalmol Vis Sci. 41. 2373-2377
- von Bartheld, CS. (1998). Neurotrophins in the developing and regenerating visual system. Histol Histopathol. 13. 437-459
- Takano, M, Horie, H, Ikjima, Y, Dezawa, M, Sawada, H, Ishikawa, Y. (2002). Brain-derived neurotrophic factor enhances neurite regeneration from retinal ganglion cells in aged human retina in vitro. Exp Eye Res. 74. 319-323
- Kashiwagi, K, Iizuka, Y, Araie, M, Suzuki, Y, Tsukahara, S. (2001). Effects of retinal glial cells on isolated rat retinal ganglion cells. Invest Ophthalmol Vis Sci. 42. 2686-2694
- Ahmed, FA, Chaudhary, P, Sharma, SC. (2001). Effects of increased intraocular pressure on rat retinal ganglion cells. Int J Dev Neurosci. 19. 209-218
- Raju, TR, Rao, MS, Nagaraja, TN, Meti, BL, Schulz, M. (1994). Retinal ganglion cell survival and neurite regeneration in vitro after cell death period are dependent upon target derived trophic factor and retinal glial factor(s). Brain Res. 664. 247-251