Abstract
• Background: It has been shown that intravitreal injection of NGF inhibits ganglion cell degeneration after optic nerve transection and ischemic injury. The aim of our study was to investigate the presence of NGF in aqueous humor and its involvement in retinal damage during ocular hypertension. • Methods: We used an experimental model of ocular hypertension in rabbit. Before treatment and 4, 10 and 15 days after induction of hypertension, we evaluated histological retinal damage and NGF levels in aqueous humor using an immunoenzymatic assay. Polyclonal anti-NGF antibodies were injected intravitreally into one eye of each rabbit (n = 6), and the animals were killed after 4 days of hypertension. Another group of rabbits (n =12) was injected retro-ocularly with NGF and killed after 10 or 15 days of treatment for histologic evaluation of the retina. • Results: Our data show that experimental ocular hypertension in adult rabbits induces retinal damage and enhances local NGF levels. The highest NGF value was found after 4 days of intraocular hypertension; high levels persisted, though to a lesser extent, for up to 15 days. Histological examination revealed that the number of retinal ganglion cells (RGC) remained unchanged during the first 4 days but decreased at 10 days. These studies also showed that retro-ocular administration of NGF reduced RGC loss, whereas intraocular injection of NGF antibodies, which inhibited the endogenous NGF, exacerbated the retinal insult. • Conclusion: These findings demonstrate a protective effect of NGF on RGC damaged by ocular hypertension and prompt further investigations to evaluate a possible therapeutic use of NGF to retard RGC death in humans.
Similar content being viewed by others
References
Ayer-Lelievre CS, Ebendal T, Olson L, Seiger A (1983) Localization of nerve growth factor-like immunoreactivity in rat nervous tissue. Med Biol 61: 296–304
Bocchini V, Angeletti PU (1968) The nerve growth factor: purification as a 30 000 molecular weight protein. Proc Natl Acad Sci USA 64:787–794
Bonfanti L, Candeo P, Piccinini M, Carmignoto G, Comelli MC, Ghidella S, Bruno R, Gobetto A, Merighi A (1992) Distribution of protein gene product 9.5 (PGP 9.5) in the vertebrate retina: evidence that immunoreactivity is restricted to mammalian horizontal and ganglion cells. J Comp Neurol 322:35–44
Bracci Laudiero L, Vigneti E, Iannicola C, Aloe L (1993) NGF retards apoptosis in chick embryo bursal cell in vitro. Differentiation 53:61–66
Carmignoto G, Maffei L, Candeo P, Canella R, Comelli C (1989) Effect of NGF on the survival of rat retinal ganglion cells following optic nerve section. J Neurosci 9:1263–1272
Carmignoto G, Comelli MC, Candeo P, Cavicchioli L, Yan Q, Merighi A, Maffei L (1991) Expression of NGF receptor mRNA in the developing and adult rat retina. Exp Neurobiol 111:302–311
Chakrabarti S, Sima AA, Lee J, Brachet P, Dcou E (1990) Nerve growth factor (NGF), proNGF and NGF receptor-like immunoreactivity in BB rat retina. Brain Res 523:11–15
Dicou E, Nerriere V, Naud MC, de Kozak Y (1994) NGF involvement in ocular inflammation: secretion by rat resident retinal cells. Neuroreport 6:26–28
Ebendal T (1992) Function and evolution in the NGF family and its receptors. J Neurosci Res 32:461–470
Ebendal T, Persson H (1988) Detection of nerve growth factor mRNA in the developing chicken embryo. Development 102:101–106
Edwards SN, Buckmaster AE, Tolkovsky AM (1991) The death programme in cultured sympathetic neurones can be suppressed at the posttranslational level by nerve growth factor, cyclic AMP and depolarization. J Neurochem 57:2140–2143
Hefti F (1994) Neurotrophic factor therapy for nervous system degenerative diseases. J Neurobiol 25:1418–1435
Heumann R, Lindholm D, Bandtlow C, Meyer M, Radeke MJ, Misko TP, Shooter E, Thoenen H (1987) Differential regulation of mRNA encoding nerve growth factor and its receptor in rat sciatic nerve during development, degeneration, and regeneration: role of macrophages. Proc Natl Acad Sci USA 84:8735–8739
Lambiase A, Aloe L (1996) Nerve growth factor delays retinal degeneration in C3H mice. Graefe's Arch Clin Exp Ophthalmol 234:596–5100
Large TH, Weskamp G, Helder JC, Radeke MJ, Misko TP, Shooter EM, Reichardt LF (1989) Structure and developmental expression of the nerve growth factor receptor in the chicken central nervous system. Neuron 2:1123–1134
La Vail MM, Unoki K, Yasumura D, Matthes MT, Yancopoulos GD, Steinberg RH (1992) Multiple growth factors, cytokines, and neurotrophins rescue photoreceptors from the damaging effects of constant light. Proc Natl Acad Sci USA 89:11249–11253
Lehwalder D, Jeffrey PL, Unsicker K (1989) Survival of purified embryonic chick retinal ganglion cells in the presence of neurotrophic factors. J Neurosci Res 24:329–337
Levi-Montalcini R (1987) The nerve growth factor 35 years later. Science 237:1154–1162
Manni GL, Lambiase A, Centofanti M, Mattei E, De Gregorio A, Aloe L, de Feo G (1996) Histopathological evaluation of retinal damage during intraocular hypertension in rabbit: involvement of ganglion cells and nerve fiber layer. Graefes Arch Clin Exp Ophthalmol 234:S209–213
Martin DP, Schmidt RE, Di Stefano PS, Lowry OH, Carter JC, Johnson EM Jr (1988) Inhibitors of protein synthesis and RNA synthesis prevent neuronal death caused by nerve growth factor deprivation. J Cell Biol 106:829–844
Olson L, Backlund EO, Ebendal T, Freedman R, Hamburger B. Hansson P, Hoffer B, Lindblom U, Meyerson B, Stromberg I, et al (1991) Intraputaminal infusion of nerve growth factor to support adrenal medullary autografts in Parkinson's disease: one-year follow-up of first clinical trial. Arch Neurol 48:373–381
Oyster CW, Takahashi ES, Hurst DC (1981) Density, soma size and regional distribution of rabbit retina ganglion cells. J Neurosci 1:1331–1346
Phelps CH, Gage FH, Growdon JH, et al (1989) Potential use of nerve growth factor to treat Alzheimer's disease. Neurobiol Aging 10:205–207
Quigley HA, Dunkelberger GR, Green WR (1989) Study of retinal ganglion cell atrophy correlated with automated perimetry in human eyes with glaucoma. Am J Ophthalmol 107:453–464
Quigley HA, Sanchez RM, Dunkelberger GR, L'Hernault NL, Baginski TA (1987) Chronic glaucoma selectively damages large optic nerve fibers. Invest Ophthalmol Vis Sci 28:913–920
Quigley HA, Nickells RW, Kerrigan LA, Pease ME, Thibault DJ, Zack DJ (1995) Retinal ganglion cell death in experimental glaucoma and after axotomy occurs by apoptosis. Invest Ophthalmol Vis Sci 36:774–786
Schwartz JP, Nishiyama N (1994) Neurotrophic factor gene expression in astrocytes during development and following injury. Brain Res Bull 35:403–407
Siliprandi R, Canella R, Carmignoto G (1993) Nerve growth factor promotes functional recovery of retinal ganglion cells after ischemia. Invest Ophthalmol Vis Sci 34:3232–3245
Steinberg RH (1994) Survival factors in retinal degenerations. Curr Opin Neurobiol 4:515–524
Strauss S, Otten U, Joggerst B, Plüss K, Volk B (1994) Increased levels of nerve growth factor (NGF) protein and mRNA and reactive gliosis following kainic acid injection into the rat striatum. Neurosci Lett 168:193–196
Vaney DI (1980) A quantitative comparison between the ganglion cell population and axonal outflows of the visual streak and periphery of the rabbit retina. J Comp Neurol 189:215–233
Weskamp G, Otten U (1987) An enzyme-linked immunoassay for nerve growth factor (NGF): a tool for studying regulatory mechanisms involved in NGF production in brain and in peripheral tissues. J Neurochem 48:1779–1786
Zhu MD, Cai FY (1992) Development of experimental chronic intraocular hypertension in the rabbit. Aust NZ J Ophthalmol 20:225–234
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lambiase, A., Centofanti, M., Micera, A. et al. Nerve growth factor (NGF) reduces and NGF antibody exacerbates retinal damage induced in rabbit by experimental ocular hypertension. Graefe's Arch Clin Exp Ophthalmol 235, 780–785 (1997). https://doi.org/10.1007/BF02332863
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02332863