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Ameliorative effect of PN-277 on laser-induced retinal damage

  • Shiri Shulman
  • Mark BelokopytovEmail author
  • Galina Dubinsky
  • Michael Belkin
  • Mordechai Rosner
Basic Science

Abstract

Background

The retinal damage induced by laser photocoagulation increases considerably by the secondary degeneration process whereby tissues adjacent to the primary lesion are destroyed. As the neuroprotective effect of immunization by PN-277 was previously demonstrated in models of retina, optic nerve, brain, and spinal cord lesions, it may be used also for reducing retinal damage induced by laser. The aim of this study was to evaluate the neuroprotective effect of immunization with PN-277 in reducing the spread of laser-induced retinal damage.

Methods

Standard argon laser lesions were created in 36 DA pigmented rats. Seven days before exposure to laser, the rats were divided into a test group (n = 18) that was pre-immunized with intraperitoneal injection of PN-277 and control group (n = 18) treated with saline. Histological and morphometrical evaluations of the retinal lesions were preformed 3, 20, and 60 days after the injury.

Results

Significant ameliorative effect was demonstrated in the retinas of the pre-immunized animals 60 days after exposure to laser. The diameter of the lesion was 356 μm as compared with 406 μm (P < 0.01), the cell density of the photoreceptor cell bodies measured in the whole lesion was 72.4% of normal as compared with 64.5% (P = 0.01), and at the center of the lesion it was 57.3% of normal as compared with 38.2% (P < 0.01) (treated and control groups, respectively).

Conclusions

Immunization with PN-277 has an ameliorative effect in neural tissue such as the retina. This type of immunization may be of clinical significance in reducing laser-induced retinal injuries in humans.

Keywords

Immunomodulation Laser injury Neuroprotection Retina Retinal injury 

References

  1. 1.
    Yoles E, Schwartz M (1998) Degeneration of spared axons following partial white matter lesion: implications for optic nerve neuropathies. Exp Neurol 153:1–7. doi: 10.1006/exnr.1998.6811 PubMedCrossRefGoogle Scholar
  2. 2.
    Kristian T, Siesjo BK (1996) Calcium-related damage in ischemia. Life Sci 59:357–367. doi: 10.1016/0024-3205(96)00314-1 PubMedCrossRefGoogle Scholar
  3. 3.
    Neufeld AH, Hernandez MR, Gonzalez M (1997) Nitric oxide synthase in the human glaucomatous optic nerve head. Arch Ophthalmol 115:497–503PubMedGoogle Scholar
  4. 4.
    Osborne NN, Chidlow G, Wood JP, Schmidt KG, Casson R, Melena J (2001) Expectations in the treatment of retinal diseases: neuroprotection. Curr Eye Res 22:321–332. doi: 10.1076/ceyr.22.5.321.5496 PubMedCrossRefGoogle Scholar
  5. 5.
    Solberg Y, Rosner M, Turetz J, Belkin M (1997) MK-801 has neuroprotective and antiproliferative effects in retinal laser injury. Invest Ophthalmol Vis Sci 38:1380–1389PubMedGoogle Scholar
  6. 6.
    Osborne NN (1999) Memantine reduces alterations to the mammalian retina, in situ, induced by ischemia. Vis Neurosci 16:45–52. doi: 10.1017/S0952523899161017 PubMedCrossRefGoogle Scholar
  7. 7.
    Moalem G, Leibowitz-Amit R, Yoles E, Mor F, Cohen IR, Schwartz M (1999) Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy. Nat Med 5:49–55. doi: 10.1038/4734 PubMedCrossRefGoogle Scholar
  8. 8.
    Kerschensteiner M, Gallmeier E, Behrens L, Leal VV, Misgeld T, Klinkert WE, Kolbeck R, Hoppe E, Oropeza-Wekerle RL, Bartke I, Stadelmann C, Lassmann H, Wekerle H, Hohlfeld R (1999) Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation? J Exp Med 1(189):865–870CrossRefGoogle Scholar
  9. 9.
    Schori H, Kipnis J, Yoles E, WoldeMussie E, Ruiz G, Wheeler LA et al (2001) Vaccination for protection of retinal ganglion cells against death from glutamate cytotoxicity and ocular hypertension: implications for glaucoma. Proc Natl Acad Sci USA 98:3398–3403. doi: 10.1073/pnas.041609498 PubMedCrossRefGoogle Scholar
  10. 10.
    Belokopytov M, Dubinsky G, Belkin M, Epstein Y, Rosner M (2005) Copolymer-1 vaccination regimens for neuroprotection in laser-induced retinal injuries. In: Manns F, Soderberg P, Ho A, Stuck BE, Belkin M (eds) Ophthalmic technologies XV. SPIE, Bellingham, Washington, USA, pp 329–336Google Scholar
  11. 11.
    Ben-Shlomo G, Belokopytov M, Rosner M, Dubinsky G, Belkin M, Epstein Y et al (2006) Functional deficits resulting from laser-induced damage in the rat retina. Lasers Surg Med 38:689–694. doi: 10.1002/lsm.20351 PubMedCrossRefGoogle Scholar
  12. 12.
    Prendiville PL, McDonnell PJ (1992) Complications of laser surgery. Int Ophthalmol Clin 32:179–204. doi: 10.1097/00004397-199223000-00012 PubMedCrossRefGoogle Scholar
  13. 13.
    Barkana Y, Belkin M (2000) Laser eye injuries. Surv Ophthalmol 44:459–478. doi: 10.1016/S0039-6257(00)00112-0 PubMedCrossRefGoogle Scholar
  14. 14.
    Liu HF, Gao GH, Wu DC, Xu GD, Shi LS, Xu JM et al (1989) Ocular injuries from accidental laser exposure. Health Phys 56:711–716PubMedCrossRefGoogle Scholar
  15. 15.
    Schwartz M, Kipnis J (2005) Protective autoimmunity and neuroprotection in inflammatory and noninflammatory neurodegenerative diseases. J Neurol Sci 233:163–166. doi: 10.1016/j.jns.2005.03.014 PubMedCrossRefGoogle Scholar
  16. 16.
    Hauben E, Nevo U, Yoles E, Moalem G, Agranov E, Mor F et al (2000) Autoimmune T cells as potential neuroprotective therapy for spinal cord injury. Lancet 355:286–287. doi: 10.1016/S0140-6736(99)05140-5 PubMedCrossRefGoogle Scholar
  17. 17.
    Schwartz M, Cohen IR (2000) Autoimmunity can benefit self-maintenance. Immunol Today 21:265–268. doi: 10.1016/S0167-5699(00)01633-9 PubMedCrossRefGoogle Scholar
  18. 18.
    Hirschberg DL, Moalem G, He J, Mor F, Cohen IR, Schwartz M (1998) Accumulation of passively transferred primed T cells independently of their antigen specificity following central nervous system trauma. J Neuroimmunol 89:88–96. doi: 10.1016/S0165-5728(98)00118-0 PubMedCrossRefGoogle Scholar
  19. 19.
    Fisher J, Levkovitch-Verbin H, Schori H, Yoles E, Butovsky O, Kaye JF et al (2001) Vaccination for neuroprotection in the mouse optic nerve: implications for optic neuropathies. J Neurosci 21:136–142PubMedGoogle Scholar
  20. 20.
    Bakalash S, Kessler A, Mizrahi T, Nussenblatt R, Schwartz M (2003) Antigenic specificity of immunoprotective therapeutic vaccination for glaucoma. Invest Ophthalmol Vis Sci 44:3374–3381. doi: 10.1167/iovs.03-0080 PubMedCrossRefGoogle Scholar
  21. 21.
    Kipnis J, Schwartz M (2002) Dual action of glatiramer acetate (Cop-1) in the treatment of CNS autoimmune and neurodegenerative disorders. Trends Mol Med 8:319–323. doi: 10.1016/S1471-4914(02)02373-0 PubMedCrossRefGoogle Scholar
  22. 22.
    Arnon R, Sela M, Teitelbaum D (1996) New insights into the mechanism of action of copolymer 1 in experimental allergic encephalomyelitis and multiple sclerosis. J Neurol 243:S8–S13. doi: 10.1007/BF00873696 PubMedCrossRefGoogle Scholar
  23. 23.
    Moalem G, Gdalyahu A, Shani Y, Otten U, Lazarovici P, Cohen IR et al (2000) Production of neurotrophins by activated T cells: Implications for neuroprotective autoimmunity. J Autoimmun 15:331–345. doi: 10.1006/jaut.2000.0441 PubMedCrossRefGoogle Scholar
  24. 24.
    Hauben E, Gothilf A, Cohen A, Butovsky O, Nevo U, Smirnov I et al (2003) Vaccination with dendritic cells pulsed with peptides of myelin basic protein promotes functional recovery from spinal cord injury. J Neurosci 23:8808–8819PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Shiri Shulman
    • 1
  • Mark Belokopytov
    • 2
    • 3
    Email author
  • Galina Dubinsky
    • 2
  • Michael Belkin
    • 2
  • Mordechai Rosner
    • 2
  1. 1.Ophthalmology DepartmentSapir Medical CentreKfar –SavaIsrael
  2. 2.Goldschleger Eye Research Institute, Sackler School of MedicineTel Aviv University, Sheba Medical CenterTel HashomerIsrael
  3. 3.Goldschleger Eye Research InstituteSheba Medical CenterTel HashomerIsrael

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