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The Decline of the Photopic Negative Response (PhNR) in the Rat after Optic Nerve Transection

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Abstract

Purpose: To investigate the contribution to the photopic negative response (PhNR) of the electroretinogram (ERG) by retinal ganglion cells (RGCs). The PhNR was assessed longitudinally following optic nerve transection (ONTx). Methods: Photopic ERGs were recorded from each eye of an anesthetized (ketamine/xylazine, 60 mg/kg and 5 mg/kg) Brown Norway rat using custom made electrodes (PT-IR Tef., A-M System Inc). ERGs were elicited using green Ganzfeld flashes (11.38 scd/m2, 22.76 cds/m2) and a rod suppressing green-background (40 cd/m2). PhNRs were compared before and after optic nerves were transected. Cresyl violet stained retinal flatmounts were used to estimate cell loss in the ganglion cell layer 3 and 15 weeks after optic nerve transection. The pharmacological effect of 1.3 μM intravitreal TTX on the PhNR was also evaluated. Results: There was a significant loss (p <0.05) in the PhNR of 20, 36, 34, 35, 48, 48 and 56% for ONTx eye versus the contralateral eye, at post ONTx times of 24 h, 1, 2, 3, 4, 8 and 15 weeks. B-wave amplitudes of ONTx eyes were not significantly different from the control eyes. In ONTx eyes, mean cell loss in the retinal ganglion cell layer was 27 and 55% at the 3 week and 15 week time periods. In the eyes with ONTx, the decline of PhNR amplitudes was correlated positively with RGC loss (r = 0.98; p < 0.01). Thirty minutes after intravitreal TTX injection, the PhNR was significantly reduced (57%, p<0.01). Conclusions: There was a time-dependent decline in the PhNR after ONTx, as exemplified by a 35% reduction from 1–3 weeks, a 48% decline for 4–8 weeks and a 56% decline after 15 weeks. The correlation between the decline in the PhNR and retinal ganglion cell loss suggests that the PhNR depends on inner retina integrity and the PhNR may be important biological signal or detecting glaucomatous damage and the monitoring of RGC function changes in early glaucoma.

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Abbreviations

PhNR:

Photopic Negative Response

ONTx:

Optic Nerve Transection

References

  1. HA Quigley RM Hohman EM Addicks RW Massof WR Green (1983) ArticleTitleMorphologic changes in the lamina cribrosa correlated with neural loss in open-angle glaucoma Am J Ophthalmol 95 673–691 Occurrence Handle1:STN:280:BiyB3c7kt1I%3D Occurrence Handle6846459

    CAS  PubMed  Google Scholar 

  2. S Viswanathan LJ Frishman JG Robson RS Harwerth EL Smith SuffixIII (1999) ArticleTitleThe photopic negative response of the macaque electroretinogram: reduction by experimental glaucoma Invest Ophthalmol Vis Sci 40 1124–1136 Occurrence Handle1:STN:280:DyaK1M3kvFKhtg%3D%3D Occurrence Handle10235545

    CAS  PubMed  Google Scholar 

  3. B Hille (1966) ArticleTitleCommon mode of action of three agents that decrease the transient change in sodium permeability in nerves Nature 210 1220–1222 Occurrence Handle1:CAS:528:DyaF28XksVWlsbk%3D Occurrence Handle5967794

    CAS  PubMed  Google Scholar 

  4. N Drasdo YH Aldebasi Z Chiti KE Mortlock JE Morgan RV North (2001) ArticleTitleS-cone PhNR and Pattern ERG in Primary Open Angle Glaucoma Invest Ophthalmol Vis Sci 42 1266–1272 Occurrence Handle1:STN:280:DC%2BD3M3kvFOjtg%3D%3D Occurrence Handle11328738

    CAS  PubMed  Google Scholar 

  5. A Colotto B Falshini T Salgarello G Iarossi ME Galan L Scullica (2000) ArticleTitlePhotopic negative response of the human erg: losses associated with glaucomatous damage Invest Ophthalmol Vis Sci 41 2205–2211 Occurrence Handle1:STN:280:DC%2BD3czkvV2msQ%3D%3D Occurrence Handle10892864

    CAS  PubMed  Google Scholar 

  6. G Trick (1986) ArticleTitlePattern reversal retinal potentials abnormalities in glaucoma and ocular hypertension Invest Ophthalmol Vis Sci 27 1730–1736 Occurrence Handle1:STN:280:BiiD1c3msF0%3D Occurrence Handle3793402

    CAS  PubMed  Google Scholar 

  7. V Porciatti B Falsini S Brunori A Colotto G Moretti (1987) ArticleTitlePattern electroretinogram as a function of spatial frequency in ocular hypertension and early glaucoma Doc Ophthalmol 65 349–355 Occurrence Handle1:STN:280:BieD2MvkvVA%3D Occurrence Handle3678006

    CAS  PubMed  Google Scholar 

  8. M Korth F Horn B Stork J Jonas (1989) ArticleTitleThe pattern evoked electroretinogram: age-related alterations and changes in glaucoma Graefes Arch Clin Exp Ophthalmol 227 123–131 Occurrence Handle1:STN:280:BiaB2M3psVc%3D Occurrence Handle2721979

    CAS  PubMed  Google Scholar 

  9. M Bach J Funk (1993) ArticleTitlePattern electroretinogram and computerized optic nerve-head analysis in glaucoma suspects Ger J Ophthalmol 2 178–181 Occurrence Handle1:STN:280:ByyA38nps1U%3D Occurrence Handle8334394

    CAS  PubMed  Google Scholar 

  10. A Hughes (1979) ArticleTitleA schematic eye for the rat Vision Res 19 569–588 Occurrence Handle1:STN:280:Bi%2BD3MrntlA%3D Occurrence Handle483586

    CAS  PubMed  Google Scholar 

  11. P Dureau S Bonnel M Menasche JL Dufier M Abitbol (2001) ArticleTitleQuantitative analysis of intravitreal injections in the rat Curr Eye Res 22 74–77 Occurrence Handle10.1076/ceyr.22.1.74.6974 Occurrence Handle1:STN:280:DC%2BD3MzjtlSlsg%3D%3D Occurrence Handle11402382

    Article  CAS  PubMed  Google Scholar 

  12. M Berkelaar DB Clarke YC Wang GM Bray AJ Aguayo (1994) ArticleTitleAxotomy results in delayed death and apoptosis of retinal ganglion cells in adult rats J Neurosci 14 4368–4374 Occurrence Handle1:STN:280:ByuA3c%2FjsFc%3D Occurrence Handle8027784

    CAS  PubMed  Google Scholar 

  13. S Thanos J Mey M Wild (1993) ArticleTitleTreatment of the adult retina with microglia-suppressing factors retards axotomy-induced neuronal degradation and enhances axonal regeneration in vivo and in vitro J Neurosci 13 455–466 Occurrence Handle1:CAS:528:DyaK3sXhvV2iur4%3D Occurrence Handle7678855

    CAS  PubMed  Google Scholar 

  14. MP Villegas-Perez M Vidal-Sanz M Rasminsky GM Bray AJ Aguayo (1993) ArticleTitleRapid and protracted phases of retinal ganglion cell loss follow axotomy in the optic nerve of adult rats J Neurobiol 24 23–36 Occurrence Handle1:STN:280:ByyC38vgtFU%3D Occurrence Handle8419522

    CAS  PubMed  Google Scholar 

  15. S Mansour-Robaey DB Clarke YC Wang GM Bray AJ Aguayo (1994) ArticleTitleEffects of ocular injury and administration of brain-derived neurotrophic factor on survival and regrowth of axotomized retinal ganglion cells Proc Natl Acad Sci USA 91 1632–1636 Occurrence Handle1:CAS:528:DyaK2cXhvVCjsLw%3D Occurrence Handle8127857

    CAS  PubMed  Google Scholar 

  16. M Russelakis-Carneiro LC Silveira VH Perry (1996) ArticleTitleFactors affecting the survival of cat retinal ganglion cells after optic nerve injury J Neurocytol 25 393–402 Occurrence Handle10.1007/BF02284810 Occurrence Handle1:CAS:528:DyaK28XltF2iurg%3D Occurrence Handle8835787

    Article  CAS  PubMed  Google Scholar 

  17. L Domenici A Gravina N Berardi L Maffei (1991) ArticleTitleDifferent effects of intracranial and intraorbital section of the optic nerve on the functional responses of rat retinal ganglion cells Exp Brain Res 86 579–584 Occurrence Handle10.1007/BF00230531 Occurrence Handle1:STN:280:By2C3cvislI%3D Occurrence Handle1761091

    Article  CAS  PubMed  Google Scholar 

  18. B Fortune BV Bui G Cull L Wang GA Cioffi (2004) ArticleTitleInter-ocular and inter-seeion reliability of the electroretinogram photopic negative response (PhNR) in non-human primates Exp Eye Res 78 83–93 Occurrence Handle10.1016/j.exer.2003.09.013 Occurrence Handle1:CAS:528:DC%2BD3sXps1erurY%3D Occurrence Handle14667830

    Article  CAS  PubMed  Google Scholar 

  19. BV Bui B Fortune (2003) ArticleTitleGanglion cell contributions to the rat full-field electroretinogram J Physiol 555 IssueID1 153–173 Occurrence Handle10.1113/jphysiol.2003.052738 Occurrence Handle14578484

    Article  PubMed  Google Scholar 

  20. S Viswanathan LJ Frishman (1997) ArticleTitleEvidence that negative potentials in the photopic electroretinograms of cats and primates depend upon spiking activity of retinal ganglion cell axons Soc Neurosci Abstr 23 1024

    Google Scholar 

  21. MP Villegas-Perez M Vidal-Sanz M Rasminsky GM Bray AJ Aguayo (1993) ArticleTitleRapid and protracted phases of retinal ganglion cell loss follow axotomy in the optic nerve of adult rats J Neurobiol. 24 23–36 Occurrence Handle1:STN:280:ByyC38vgtFU%3D Occurrence Handle8419522

    CAS  PubMed  Google Scholar 

  22. Y Fukuda (1977) ArticleTitleA three-group classification of rat retinal ganglion cells: histological and physiological studies Brain Res 119 327–334 Occurrence Handle10.1016/0006-8993(77)90314-6 Occurrence Handle1:STN:280:CSiD28njvFE%3D Occurrence Handle830390

    Article  CAS  PubMed  Google Scholar 

  23. J Mey S Thanos (1993) ArticleTitleIntravitreal injections of neurotrophic factors support the survival of axotomized retinal ganglion cells in adult rats in vivo Brain Res 602 304–317 Occurrence Handle10.1016/0006-8993(93)90695-J Occurrence Handle1:CAS:528:DyaK3sXhtFOnur8%3D Occurrence Handle8448673

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Alcon Research Ltd., Fort Worth, TX, USA

    B. Li, G. E. Barnes & W. F. Holt

  2. Alcon Research Ltd., R9-11, 6201 South FWY, Fort Worth, TX, 76134, USA

    B. Li

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  1. B. Li
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  2. G. E. Barnes
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Correspondence to B. Li.

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Li, B., Barnes, G.E. & Holt, W.F. The Decline of the Photopic Negative Response (PhNR) in the Rat after Optic Nerve Transection. Doc Ophthalmol 111, 23–31 (2005). https://doi.org/10.1007/s10633-005-2629-8

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  • DOI: https://doi.org/10.1007/s10633-005-2629-8

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