Skip to main content
SpringerLink
Log in

Alterations of Sodium and Potassium Channels of RGCs in RCS Rat with the Development of Retinal Degeneration

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

All know that retinitis pigmentosa (RP) is a group of hereditary retinal degenerative diseases characterized by progressive dysfunction of photoreceptors and associated with progressive cells loss; nevertheless, little is known about how rods and cones loss affects the surviving inner retinal neurons and networks. Retinal ganglion cells (RGCs) process and convey visual information from retina to visual centers in the brain. The healthy various ion channels determine the normal reception and projection of visual signals from RGCs. Previous work on the Royal College of Surgeons (RCS) rat, as a kind of classical RP animal model, indicated that, at late stages of retinal degeneration in RCS rat, RGCs were also morphologically and functionally affected. Here, retrograde labeling for RGCs with Fluorogold was performed to investigate the distribution, density, and morphological changes of RGCs during retinal degeneration. Then, patch clamp recording, western blot, and immunofluorescence staining were performed to study the channels of sodium and potassium properties of RGCs, so as to explore the molecular and proteinic basis for understanding the alterations of RGCs membrane properties and firing functions. We found that the resting membrane potential, input resistance, and capacitance of RGCs changed significantly at the late stage of retinal degeneration. Action potential could not be evoked in a part of RGCs. Inward sodium current and outward potassium current recording showed that sodium current was impaired severely but only slightly in potassium current. Expressions of sodium channel protein were impaired dramatically at the late stage of retinal degeneration. The results suggested that the density of RGCs decreased, process ramification impaired, and sodium ion channel proteins destructed, which led to the impairment of electrophysiological functions of RGCs and eventually resulted in the loss of visual function.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  • Chen S, Diamond JS (2002) Synaptically released glutamate activates extrasynaptic NMDA receptors on cells in the ganglion cell layer of rat retina. J Neurosci 22:2165–2173

    PubMed  CAS  Google Scholar 

  • Chen ZS, Yin ZQ, Chen S, Wang SJ (2005) Electrophysiological changes of retinal ganglion cells in Royal College of Surgeons rats during retinal degeneration. Neuroreport 16:971–975

    Article  PubMed  Google Scholar 

  • Coffey PJ, Girman S, Wang SM, Hetherington L, Keegan DJ, Adamson P, Greenwood J, Lund RD (2002) Long-term preservation of cortically dependent visual function in RCS rats by transplantation. Nat Neurosci 5:53–56

    Article  PubMed  CAS  Google Scholar 

  • da Cruz L, Chen FK, Ahmado A, Greenwood J, Coffey P (2007) RPE transplantation and its role in retinal disease. Prog Retin Eye Res 26:598–635

    Article  PubMed  Google Scholar 

  • Dann JF, Buhl EH (1987) Retinal ganglion cells projecting to the accessory optic system in the rat. J Comp Neurol 262:141–158

    Article  PubMed  CAS  Google Scholar 

  • DeMarco PJ Jr, Yarbrough GL, Yee CW, McLean GY, Sagdullaev BT, Ball SL, McCall MA (2007) Stimulation via a subretinally placed prosthetic elicits central activity and induces a trophic effect on visual responses. Invest Ophthalmol Vis Sci 48:916–926

    Article  PubMed  Google Scholar 

  • Demb JB, Haarsma L, Freed MA, Sterling P (1999) Functional circuitry of the retinal ganglion cell's nonlinear receptive field. J Neurosci 19:9756–9767

    PubMed  CAS  Google Scholar 

  • Dubin MW, Stark LA, Archer SM (1986) A role for action-potential activity in the development of neuronal connections in the kitten retinogeniculate pathway. J Neurosci 6:1021–1036

    PubMed  CAS  Google Scholar 

  • Felmy F, Pannicke T, Richt JA, Reichenbach A, Guenther E (2001) Electrophysiological properties of rat retinal Muller (glial) cells in postnatally developing and in pathologically altered retinae. Glia 34:190–199

    Article  PubMed  CAS  Google Scholar 

  • Fukuda A, Prince DA (1992) Postnatal development of electrogenic sodium pump activity in rat hippocampal pyramidal neurons. Brain Res 65:101–114

    Article  CAS  Google Scholar 

  • Griessmeier K, Cuny H, Rotzer K, Griesbeck O, Harz H, Biel M, Wahl-Schott C (2009) Calmodulin is a functional regulator of Cav1.4 L-type Ca2+ channels. J Biol Chem 284:29809–29816

    Article  PubMed  CAS  Google Scholar 

  • Guenther E, Schmid S, Reiff D, Zrenner E (1999) Maturation of intrinsic membrane properties in rat retinal ganglion cells. Vision Res 39:2477–2484

    Article  PubMed  CAS  Google Scholar 

  • Huang YM, Yin ZQ, Liu K, Huo SJ (2011) Temporal and spatial characteristics of cone degeneration in RCS rats. Jpn J Ophthalmol 55:155–162

    Article  PubMed  Google Scholar 

  • Humayun MS, Prince M, de Juan E Jr, Barron Y, Moskowitz M, Klock IB, Milam AH (1999) Morphometric analysis of the extramacular retina from postmortem eyes with retinitis pigmentosa. Invest Ophthalmol Vis Sci 40:143–148

    PubMed  CAS  Google Scholar 

  • Huxlin KR, Goodchild AK (1997) Retinal ganglion cells in the albino rat: revised morphological classification. J Comp Neurol 385:309–323

    Article  PubMed  CAS  Google Scholar 

  • Iandiev I, Biedermann B, Bringmann A, Reichel MB, Reichenbach A, Pannicke T (2006) Atypical gliosis in Muller cells of the slowly degenerating RDS mutant mouse retina. Exp Eye Res 82:449–457

    Article  PubMed  CAS  Google Scholar 

  • Lagali PS, Balya D, Awatramani GB, Munch TA, Kim DS, Busskamp V, Cepko CL, Roska B (2008) Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration. Nat Neurosci 11:667–675

    Article  PubMed  CAS  Google Scholar 

  • Lasater EM (1988) Membrane currents of retinal bipolar cells in culture. J Neurophysiol 60:1460–1480

    PubMed  CAS  Google Scholar 

  • Manookin MB, Demb JB (2006) Presynaptic mechanism for slow contrast adaptation in mammalian retinal ganglion cells. Neuron 50:453–464

    Article  PubMed  CAS  Google Scholar 

  • Margolis DJ, Newkirk G, Euler T, Detwiler PB (2008) Functional stability of retinal ganglion cells after degeneration-induced changes in synaptic input. J Neurosci 28:6526–6536

    Article  PubMed  CAS  Google Scholar 

  • Mazzoni F, Novelli E, Strettoi E (2008) Retinal ganglion cells survive and maintain normal dendritic morphology in a mouse model of inherited photoreceptor degeneration. J Neurosci 28:14282–14292

    Article  PubMed  CAS  Google Scholar 

  • Mergler S, Steinhausen K, Wiederholt M, Strauss O (1998) Altered regulation of L-type channels by protein kinase C and protein tyrosine kinases as a pathophysiologic effect in retinal degeneration. FASEB J 12:1125–1134

    PubMed  CAS  Google Scholar 

  • Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic Press, San Diego, pp 50–56

  • Pinilla I, Lund RD, Sauve Y (2005) Cone function studied with flicker electroretinogram during progressive retinal degeneration in RCS rats. Exp Eye Res 80:51–59

    Article  PubMed  CAS  Google Scholar 

  • Pu M, Xu L, Zhang H (2006) Visual response properties of retinal ganglion cells in the royal college of surgeons dystrophic rat. Invest Ophthalmol Vis Sci 47:3579–3585

    Article  PubMed  Google Scholar 

  • Reiff DF, Guenther E (1999) Developmental changes in voltage-activated potassium currents of rat retinal ganglion cells. Neuroscience 92:1103–1117

    Article  PubMed  CAS  Google Scholar 

  • Sauve Y, Girman SV, Wang S, Keegan DJ, Lund RD (2002) Preservation of visual responsiveness in the superior colliculus of RCS rats after retinal pigment epithelium cell transplantation. Neuroscience 114:389–401

    Article  PubMed  CAS  Google Scholar 

  • Stasheff SF (2008) Emergence of sustained spontaneous hyperactivity and temporary preservation of OFF responses in ganglion cells of the retinal degeneration (rd1) mouse. J Neurophysiol 99:1408–1421

    Article  PubMed  Google Scholar 

  • Sun W, Li N, He S (2002) Large-scale morphological survey of rat retinal ganglion cells. Vis Neurosci 19:483–493

    PubMed  Google Scholar 

  • Tomita H, Sugano E, Yawo H, Ishizuka T, Isago H, Narikawa S, Kugler S, Tamai M (2007) Restoration of visual response in aged dystrophic RCS rats using AAV-mediated channelopsin-2 gene transfer. Invest Ophthalmol Vis Sci 48:3821–3826

    Article  PubMed  Google Scholar 

  • Wang S, Lu B, Girman S, Holmes T, Bischoff N, Lund RD (2008) Morphological and functional rescue in RCS rats after RPE cell line transplantation at a later stage of degeneration. Invest Ophthalmol Vis Sci 49:416–421

    Google Scholar 

  • Wang SJ, Xie LH, Heng B, Liu YQ (2012) Classification of potassium and chlorine ionic currents in retinal ganglion cell line (RGC-5) by whole-cell patch clamp. Vis Neurosci 29:275–282

    Article  PubMed  Google Scholar 

  • Wollner DA, Scheinman R, Catterall WA (1988) Sodium channel expression and assembly during development of retinal ganglion cells. Neuron 1:727–737

    Article  PubMed  CAS  Google Scholar 

  • Zhang L, Spigelman I, Carlen PL (1991) Development of GABA-mediated, chloride-dependent inhibition in CA1 pyramidal neurones of immature rat hippocampal slices. J Physiol 444:25–49

    PubMed  CAS  Google Scholar 

  • Zhang CX, Yin ZQ, Chen LF, Weng CH, Zeng YX (2010) ON-retinal bipolar cell survival in RCS rats. Curr Eye Res 35:1002–1011

    PubMed  Google Scholar 

  • Zhang CX, Yin ZQ, Weng CH, Zeng YX (2011) The modification of electrophysiology affected by ectopic synapse in ON-retinal bipolar cells of RCS rats. Chin J Ophthalmol 47:210–216

    Google Scholar 

Download references

Acknowledgments

This work was supported by the Nature Science Foundation of China Grant, Major International (Regional) Joint Research Project 30910103913 (to Zhengqin Yin and Gillies Mark) and the Nature Science Foundation of China Grant 30900446 (to Zhongshan Chen). The authors thank Professor Matthew M. LaVail of UCSF for charitably presenting RCS rats. We also thank Madam Wei Sun (from Central Lab of Third Military Medical University) for confocal microscopy and Miss Yuxiao Zeng for technical assistance.

Author information

Authors and Affiliations

  1. Southwest Hospital, Southwest Eye Hospital, Third Military Medical University, Chongqing, 400038, China

    Zhongshan Chen, Chuanhuang Weng & Zheng Qin Yin

  2. Department of Ophthalmology, Wuhan General Hospital of Guangzhou Military Command, Wuhan, 430070, China

    Zhongshan Chen & Yanping Song

  3. Department of Ophthalmology, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, 430000, China

    Junping Yao

Authors
  1. Zhongshan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yanping Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Junping Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chuanhuang Weng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zheng Qin Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zheng Qin Yin.

Additional information

Z. Chen and Z. Yin contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, Z., Song, Y., Yao, J. et al. Alterations of Sodium and Potassium Channels of RGCs in RCS Rat with the Development of Retinal Degeneration. J Mol Neurosci 51, 976–985 (2013). https://doi.org/10.1007/s12031-013-0082-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-013-0082-9

Keywords

Search

Navigation